- C-(2-chloroquinoline-3-yl)-N-phenyl nitrone: New synthetic antioxidant inhibits proliferation and induces apoptosis of breast carcinoma MCF-7 cells
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In this work, a new quinoline nitrone derivative, C-(2-chloroquinoline-3- yl)-N-phenyl nitrone (CQPN) was successfully prepared and proved by spectral analysis. The antioxidant activity of CQPN against various radicals was investigated and its anti-cancer
- Ramadan, Mohamed,Gamal-Eldeen, Amira M.,Abdel-Aziz, Mohamed,Abuo-Rahma, Gamal El-Din,Abdel-Nabi, Hisham,Nagib, Abdel-Hamid
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- Synthesis of some complex pyrano[2,3-b]- and pyrido[2,3-b]quinolines from simple acetanilides via intramolecular domino hetero Diels-Alder reactions of 1-oxa-1,3-butadienes in aqueous medium
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Some complex pyrano[2,3-b]- and pyrido[2,3-b]quinolines were synthesized from simple acetanilides via intramolecular domino hetero Diels-Alder reactions of 1-oxa-1,3-butadienes using water as solvent.
- Baruah, Biswajita,Bhuyan, Pulak J.
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- A novel fluorescent chemosensor for Zn(II) based on 1,2-(2′-oxoquinoline-3′-yl-methylideneimino)ethane
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A new bis Schiff-base ligand (1,2-(2′-oxoquinoline-3′-yl-methylideneimino)ethane, QSB) derived from 2-oxo-quinoline-3-carbaldehyde and ethylene diamine was synthesized and characterized by 1H-NMR. Spectroscopic investigation revealed that the compound exhibited a high selectivity toward Zn(II) ion over other metal ions in acetonitrile solution. In addition, the crystal structure showed that the coordination form of QSB and Zn(II) was 1:1.
- Liu, Zeng-chen,Wang, Bao-dui,Yang, Zheng-yin,Li, Tian-rong,Li, Yong
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- Indium chloride/silica gel supported synthesis of pyrano/thiopyranoquinolines through intramolecular imino Diels-Alder reaction using microwave irradiation
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A facile synthesis of pyrano/thiopyranoquinolines is accomplished in excellent yields through imino Diels-Alder reaction using silica gel impregnated with indium trichloride as catalyst.
- Ramesh, Ekambaram,Sree Vidhya, Tarakkad Krishnaji,Raghunathan, Raghavachary
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- Efficient synthesis of quinolo-oxepanes through [3+2] cycloaddition reaction of α,β-unsaturated ester with unstabilized azomethine ylides
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New functionalized quinolo-oxepane were achieved by intramolecular 1,3-dipolar cycloaddition reaction of α,β-unsaturated ester with unstabilized azomethine ylides derived from various α-amino acids with high stereo selectivity and good yields. These deriv
- Saravanan, Nagarajan,Arthanareeswari, Maruthapillai,Kamaraj, Palanisamy,Sivakumar, Bitragunta
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- One-pot three-component synthesis of 2H-thiopyrano[2,3-b]quinoline-2,3-dicarboxylates from 2-mercaptoquinoline-3-carbaldehydes, dialkyl acetylenedicarboxylates and Ph3P
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An extremely concise one-pot procedure toward the synthesis of 2H-Thiopyrano [2,3-b]quinoline-2,3-dicarboxylates whose applications as medicines is predictable has been established. This approach produces three fused rings evolving from the formation of four new carbon–carbon bonds and a stereogenic center in a one-pot protocol.
- Alizadeh, Abdolali,Roosta, Atefeh,Amir Ashjaee Asalemi, Kaveh
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- Visible light induced nano copper catalyzed one pot synthesis of novel quinoline bejeweled thiobarbiturates as potential hypoglycemic agents
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An efficient visible light induced one pot three component approach for the synthesis of new quinoline bejeweled thiobarbiturates via Knoevenagel condensation and N-alkylation using copper nanoparticles (CuNPs) have been reported. These copper nanoparticles due to their diverse properties, smaller size (50–100 nm), and high surface area to volume ratio exhibit promising features for the reaction response such as the shorter reaction time, simple work-up procedure, clean reaction profiles, and excellent product yields through reusability of the catalyst upto five cycles. The recovered catalyst was successfully characterized by EDAX and AFM analysis. In silico molecular docking studies were carried out to find out the effective binding affinity of the synthesized quinoline derivatives toward PPARγ protein. The results obtained showed that compounds 4d, 4e, and 4f possess good binding interaction toward PPARγ with binding energy of ?7.4, ?7.2 and, ?7.6 k.cal/mol which was greater than standard rosiglitazone (?6.4 k.cal/mol) and comparable to that of standard pioglitazone (?7.9 k.cal/mol). In vitro α-amylase and α-glucosidase assays were performed for hypoglycemic activity evaluation. The compounds 4e and 4f at a concentration of 100 μg/ml showed 82.13% and 83.26% inhibition toward α-glucosidase, 78.30% and 84.18% inhibition toward α-amylase which was higher than standard pioglitazone and on par to that of rosiglitazone and acarbose.
- Angajala, Gangadhara,Aruna, Valmiki,Subashini, Radhakrishnan
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- α-cyclisation of tertiary amines: Synthesis of some novel annelated quinolines via a three-component reaction under solvent-free conditions
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Synthesis of some novel classes of quinolizine-, indolizine- and pyrido-1,4-oxazine-fused quinoline derivatives via a three-component reaction under solvent-free conditions by exploring the 'tertiary amine effect' reaction strategy. Georg Thieme Verlag Stuttgart.
- Devi, Ipsita,Baruah, Biswajita,Bhuyan, Pulak J.
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- Hydrolysis of phosphoryl trichloride (POCl3): Characterization, in situ detection, and safe quenching of energetic metastable intermediates
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The accumulation of metastable intermediates resulting from the incomplete hydrolysis of phosphoryl trichloride-containing mixtures carries the risk of latent exothermic events. Significant accumulation of two P-Cl species containing reactive phosphorus-c
- Achmatowicz, Micha M.,Thiel, Oliver R.,Colyer, John T.,Tomaskevitch, Joe,Tedrow, Jason S.,Larsen, Robert D.,Hu, Jack,Elipe, Maria Victoria Silva
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- Crystal structures, DNA-binding and cytotoxic activities studies of Cu(II) complexes with 2-oxo-quinoline-3-carbaldehyde Schiff-bases
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Three novel 2-oxo-quinoline-3-carbaldehyde Schiff-bases and their Cu(II) complexes were synthesized. The molecular structures of Cu(II) complexes were determined by X-ray crystal diffraction. The DNA-binding modes of the complexes were also investigated b
- Liu, Zeng-Chen,Wang, Bao-Dui,Li, Bo,Wang, Qin,Yang, Zheng-Yin,Li, Tian-Rong,Li, Yong
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- Design, synthesis, anticancer, antimicrobial activities and molecular docking studies of novel quinoline bearing dihydropyridines
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A new series of eight quinoline bearing dihydropyridine derivatives (A1–A8) were synthesized in high yield and in short reaction time by a four component reaction of 2-chloro-3-fomyl quinoline, malononitrile, arylamines and dimethyl acetylenedicarboxylate in the presence of a catalytic amount of triethylamine. The compounds were fully characterized by IR, NMR and GC–MS. These compounds were screened for potential biological activity in an A549 lung cancer cell line and were also evaluated for their antibacterial activities against Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 29213 whilst their molecular docking properties in an enzymatic system were also determined. Compounds A2, A3, A4 and A8 showed anti-proliferative activity; with A4 having the highest toxicity at 250 μg/mL and A8 has high toxicity at 125, 250 and 500 μg/mL, respectively. Antibacterial results indicated that A4 have significant activity against tested microorganisms at the minimum inhibitory concentration (MIC) values of 32 μg/mL against Pseudomonas aeruginosa and Escherichia coli, and 16 μg/mL against Staphylococcus aureus. Docking of A1 with human mdm2 indicated the lowest binding energy (? 6.111 Kcal/mol) thereby showing strong affinity of the ligand molecule with the receptor which has been stabilized by strong hydrogen bond interactions in the binding pocket. This confirms that A1 is a better inhibitor for E3 ubiquitin-protein ligase mdm2.
- Nkosi, S'busiso Mfan'vele,Anand, Krishnan,Anandakumar,Singh, Sanil,Chuturgoon, Anil Amichund,Gengan, Robert Moonsamy
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- Preparation and characterization of rod-like chitosan–quinoline nanoparticles as pH-responsive nanocarriers for quercetin delivery
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Novel chitosan–quinoline nanoparticles as anticancer drug nanocarriers were prepared using 2-chloro-3-formylquinoline and 3-formylquinolin-2(1H)-one as non-toxic modifying agents via oil–in–water nanoemulsion technique. Chitosan–quinoline nanoparticles were characterized by FT–IR, UV–vis spectrophotometry, XRD, SEM, AFM and DLS techniques. The morphological and particle size studies demonstrated that drug–loaded chitosan–quinoline nanoparticles have a regular nanorod shape and monolithic structure with the desired particle size of 141 to 174.8 nm and a negative zeta potential of ?2.4 to ?14.1 mV. Drug loading capacity (LC) and encapsulation efficiency (EE) were achieved using quercetin as a hydrophobic anticancer drug and were about 4.8–9.6% and 65.8–77%, respectively. The in vitro release studies displayed great pH-sensitive release behavior. Evaluation of the anticancer efficacy of quercetin loaded chitosan–quinoline nanoparticles using the in vitro cytotoxicity studies against HeLa cells indicated that the chitosan nanoparticles are a promising candidate for the anticancer drugs delivery.
- Rahimi, Shahnaz,Khoee, Sepideh,Ghandi, Mehdi
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- An effective Cu(ii) quenching fluorescence sensor in aqueous solution and 1D chain coordination polymer framework
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In the article, a novel fluorescent probe for the copper cation based on fluorescence quenching mechanism was designed. It exhibited high selectivity for Cu(ii) over other common metal ions in aqueous media. Furthermore the coordination between Cu(ii) and the organic molecule sensor fabricated an interesting 1D chain coordination polymer framework.
- Liu, Zeng-Chen,Yang, Zheng-Yin,Li, Tian-Rong,Wang, Bao-Dui,Li, Yong,Qin, Dong-Dong,Wang, Ming-Fang,Yan, Mi-Hui
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- Synthesis, characterization and anticonvulsant potential of 2,5-disubstituted 1,3,4-oxadiazole analogues
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A new series of compounds in which benzimidazole, oxadiazole and quinoline were incorporated, was synthesized and investigated for their anticonvulsant activity. Some of the newly synthesized compounds have shown good anticonvulsant activity. Significant
- Kumar, Rajnish,Abdullah, Mohd Mustaqeem
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- Synthesis of new quinoline derivatives
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The synthesis of some new functionalized quinolyl derivatives has been described, based on the 1,3-dipolar cycloaddition of an azomethine ylide, generated from sarcosine or N-benzylglycine and paraformaldehyde, to 2-chloro-3-quinolinecarbaldehydes. Copyright Taylor & Francis Group, LLC.
- Toth, Judit,Blasko, Gabor,Dancso, Andras,Toke, Laszlo,Nyerges, Miklos
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- Design and synthesis of novel quinoline derivatives bearing oxadiazole, isoxazoline, triazolothiadiazole, triazolothiadiazine, and piperazine moieties
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A new series of 2,3-disubstituted quinoline derivatives were synthesized from 2-chloroquinoline-3-carbaldehyde. In the reaction sequence, acetanilide was cyclized to give 2-chloroquinoline-3-carbaldehyde 1, which was transformed to 2-(4-phenylpiperazin-1-yl)quinolin-3-carbaldehyde 2 by reaction with 4-phenylpiperazine in DMF-containing anhydrous K2CO3; then, compound 2 was oxidized by iodine in methanol, and methyl 2-(4-phenylpiperazin-1-yl)quinoline-3-carboxylate 3 was synthesized. The key intermediate 4, 4-amino-5-[2-(4-phenylpiperazin-1-yl)quinolin-3-yl]-4H-1,2,4-triazole-3-thiol, was prepared using the ester 3 by a series of step. Reaction of 5 with various aromatic carboxylic acids or phenacyl bromides yielded 1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles 5a-c and 1,2,4-triazolo[3,4-b][1,3,4]thiadiazines 6a-c, respectively. Moreover, compound 2 condensed with o-phenylenediamine to give 2-[2-(4-phenylpiperazin-1-yl)quinolin-3-yl]-1H-benzimidazole 7. Interaction of 7 and 2-chloromethyl-5-aryl-1,3,4-oxadiazoles in the presence of K2CO3 led to the title compounds 8a-c. Furthermore, 4,5-dihydroisoxazoline derivatives 9a-c were obtained by the reaction of readily accessible starting materials including 2-(4-phenylpiperazin-1-yl)quinolin-3-carbaldehyde 2, 1-phenyl-2-(triphenylphosphoranylidene)ethanone and hydroximoyl chlorides under mild conditions in the presence of Et3N. The hydrazone intermediates 10a-c were obtained by the condensation of 2 with aroylhydrazides in ethanol, then, refluxing in acetic anhydride yielded 3-acetyl-5-aryl-2-[2-(4-phenylpiperazin-1-yl)quinolin-3-yl]-2,3-dihydro-1,3,4-oxadiazoles 11a-c. Structures of these compounds were established by their elemental analysis, IR, 1H NMR, and mass spectral data.
- Tang, Zhiren,Peng, Yang,Liu, Fangming
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- Synthesis and biological evaluation of novel 2-arylquinoline-3-fused thiazolo[2,3-c]1,2,4-triazole heterocycles as potential antiproliferative and antimicrobial agents
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A series of novel 2-arylquinoline-3-fused thiazolo[2,3-c]1,2,4-triazole heterocycles 9a-t were efficiently synthesized using simple conventional methods in good yields. The structure of newly synthesized molecules was characterized on the basis of their IR, 1H NMR, 13C NMR and mass spectral data. Among 9a-t, compounds 9h, 9n, 9b and 9d exhibited highly significant antiproliferative activity against two cancer cell lines C6 (nerve cells) and MCF-7 (human breast adenocarcinoma cells) when compared with standard reference Doxorubicin. In vitro antimicrobial activities of target compounds 9h, 9b, 9d, 9m and 9n were effectuated on Gram-positive Staphylococcus aurus (ATCC 25923), Bacillus subtilis (ATCC 6633) and Gram-negative strains Klebsiella Pneumonia (ATCC 31488) and Escherichia coli (ATCC 25966) strains and found to exhibit promising activity against standard Ciprofloxacin drug. Further, when in vitro antifungal activity was conducted on Aspergillus flavus and Aspergillus niger strains 9h, 9b, 9d and 9n were exhibited potent activity when compared with standard Fluconazole drug moiety.
- Atcha, Krishnam Raju,Birdaraju, Saritha,Bitla, Sampath,Dhanavath, Ramulu,Dharavath, Ravinder,Kothula, Devender,Puchakayala, Muralidhar Reddy,Yaku, Gugulothu
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- Design, synthesis and biological evaluation of mono- and bisquinoline methanamine derivatives as potential antiplasmodial agents
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Several classes of antimalarial drugs are currently available, although issues of toxicity and the emergence of drug resistant malaria parasites have reduced their overall therapeutic efficiency. Quinoline based antiplasmodial drugs have unequivocally been long-established and continue to inspire the design of new antimalarial agents. Herein, a series of mono- and bisquinoline methanamine derivatives were synthesised through sequential steps; Vilsmeier-Haack, reductive amination, and nucleophilic substitution, and obtained in low to excellent yields. The resulting compounds were investigated for in vitro antiplasmodial activity against the 3D7 chloroquine-sensitive strain of Plasmodium falciparum, and compounds 40 and 59 emerged as the most promising with IC50 values of 0.23 and 0.93 μM, respectively. The most promising compounds were also evaluated in silico by molecular docking protocols for binding affinity to the {0 0 1} fast-growing face of a hemozoin crystal model.
- Bokosi, Fostino R.B.,Beteck, Richard M.,Mbaba, Mziyanda,Mtshare, Thanduxolo E.,Laming, Dustin,Hoppe, Heinrich C.,Khanye, Setshaba D.
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supporting information
(2021/03/01)
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- Arylquinolinecarboxamides: Synthesis, in vitro and in silico studies against Mycobacterium tuberculosis
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A series of fourteen 6-substituted-2-(methoxyquinolin-3-yl) methyl)-N-(pyridin-3-ylmethyl) benzamides was prepared from commercially available anilines in five simple and convenient synthetic steps. The structures of all new products were confirmed by routine spectroscopic methods: IR, 1H and 13C NMR, and HRMS (electrospray ionization). The resulting arylquinolinecarboxamides were subjected to biological screening assay for in vitro inhibitory activity against Mycobacterium tuberculosis (Mtb) H37Rv strain. Several compounds exhibited modest antitubercular activity with compounds 8–11, 15 and 19 exhibiting MIC90 values in the range of 32–85 μM. The antitubercular data suggested that inhibition of Mtb can be imparted by the introduction of a non-polar substituent on C-6 of the quinoline scaffold. Further, to understand the possible mode of action of the series, the reported compounds and bedaquiline were subjected to in silico docking studies against MtbATPase to determine their potential to interfere with the mycobacterial adenosine triphosphate (ATP) synthase. The results showed that these compounds have the potential to serve as antimycobacterial agents. In silico ADME pharmacokinetic prediction results showed the ability of these arylquinolinecarcboxamides to be absorbed, distributed, metabolized and excreted efficiently.
- Bokosi, Fostino R. B.,Beteck, Richard M.,Jordaan, Audrey,Seldon, Ronnet,Warner, Digby F.,Tshiwawa, Tendamudzimu,Lobb, Kevin,Khanye, Setshaba D.
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supporting information
p. 2140 - 2151
(2021/07/21)
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- New 3-(1H-benzo[d]imidazol-2-yl)quinolin-2(1H)-one-based triazole derivatives: Design, synthesis, and biological evaluation as antiproliferative and apoptosis-inducing agents
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A series of 1,2,3-triazole derivatives based on the quinoline–benzimidazole hybrid scaffold was designed, synthesized, and screened against a panel of NCI-60 humanoid cancer cell lines for in vitro cytotoxicity evaluation, which revealed that compound Q6 was the most potent cytotoxic agent with excellent GI50, TGI, and LC50 values on multiple cancer cell lines. Q6 was tested further on the BT-474 breast cancer line to evaluate the mechanism of action. Preliminary screening studies based on the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay revealed that compound Q6 had an excellent antiproliferative effect against human breast cancer cells, BT-474, with IC50 values of 0.59 ± 0.01 μM. The detailed study based on the acridine orange/ethidium bromide staining (AO/EB) and the 4′,6-diamidino-2-phenylindole (DAPI) assay suggested that the antiproliferative activity shown was due to the induction of apoptosis on exposure to Q6. Further, DCFDA staining showed the generation of reactive oxygen species, altering the mitochondrial potential and leading to the initiation of apoptosis. This was further supported by JC-1 staining, indicating that this scaffold can contribute to the development of more potent derivatives.
- Gaikwad, Nikhil B.,Bansode, Sapana,Biradar, Shankar,Ban, Mayuri,Srinivas, Nanduri,Godugu, Chandraiah,Yaddanapudi, Venkata M.
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- Design, synthesis and evaluation of novel β-carboline ester analogues as potential anti-leishmanial agents
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Leishmaniasis is one of today's most neglected diseases. The emergence of new anti-leishmanial therapies emphasizes several study groups funded by the World Health Organization. The present investigation will focus on the research to determine a few new potential derivatives of β-carboline ester derivatives against leishmaniasis. The in-silico predicted ADMET properties of most of the titled compounds are in an acceptable range and having drug like properties. Among all the tested analogs, compound ES-3 (EC50 3.36 μM; SI > 29.80) showed comparable and equipotent anti-leishmanial activity as that of standard drug miltefosine (EC50 4.80 μM; SI > 20.80) against amastigote forms of the tested L. infantum strain. Two compounds ES-6 and ES-10 exhibited significant activity with EC50 10.16, 13.56 μM; SI > 4.90, 7.37, respectively. In-silico based molecular docking and dynamics study of the significantly active analog also performed to study the putative binding mode, interaction pattern at the active site of the target leishmanial trypanothione reductase enzyme as well as stability of the target-ligand complex. The changes in the conformation of molecules during MD (frame wise trajectory analysis) provided new insights for the development of novel potent molecules. These findings will further give insight that will help modify the compound ES-3 for better potency and the design of novel inhibitors for leishmaniasis. Communicated by Ramaswamy H. Sarma.
- Adinarayana, Nandikolla,Balana Fouce, Rafael,Chandra Sekhar, K. V. G.,Faheem,Karan Kumar, Banoth,Melcon-Fernandez, Estela,Murugesan, Sankaranarayan,Perez-Pertejo Yolanda, Yolanda,Reguera, Rosa M.,Vanaparthi, Satheeshvarma
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- Cytotoxic triterpenoid–safirinium conjugates target the endoplasmic reticulum
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Safirinium P and Q fluorescence labels were synthesized and conjugated with spacered triterpenoic acids to access hybrid structures. While the parent safirinium compounds were not cytotoxic at all, many triterpenoid safirinium P and Q conjugates showed moderate cytotoxicity. An exception, however, was safirinium P derived compound 30 holding low EC50 = 5.4 μM (for A375 cells) to EC50 = 7.5 μM (for FaDu cells) as well as EC50 = 6.6 μM for non-malignant fibroblasts NIH 3T3. Fluorescence imaging showed that the safirinium core structures cannot enter the cells (not even after a prolonged incubation time of 24 h), while the conjugates (as exemplified for 30) are accumulating in the endoplasmic reticulum but not in the mitochondria. The development of safirinium–hybrids targeting the endoplasmic reticulum can be regarded as a promising strategy in the development of cytotoxic agents.
- Kraft, Oliver,Kozubek, Marie,Hoenke, Sophie,Serbian, Immo,Major, Daniel,Csuk, René
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- Synthesis and Evaluation of the Antibacterial and Antioxidant Activities of Some Novel Chloroquinoline Analogs
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Quinoline heterocycle is a useful scaffold to develop bioactive molecules used as anticancer, antimalaria, and antimicrobials. Inspired by their numerous biological activities, an attempt was made to synthesize a series of novel 7-chloroquinoline derivati
- Abdi, Bayan,Eswaramoorthy, Rajalakshmanan,Fekadu, Mona,Melaku, Yadessa,Zeleke, Digafie
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- Synthesis of indenoquinolinone through aryne-mediated Pd(II)-catalysed remote C–H activation
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Abstract: [Figure not available: see fulltext.]Indenoquinolinones have been synthesized from 2-haloquinoline-3-carbaldehyde through Pd-mediated simultaneous C–H (aldehyde) and C–X bond activation. DFT studies were performed to investigate the mechanistic pathway, and in situ UV–Vis studies indicate the presence of Pd(II) intermediate species. Aryne ligated Pd complex is actual intermediate in these reactions. Ligation of reactive aryne to Pd reduces probability of side reactions. Graphic abstract: [Figure not available: see fulltext.]
- Patel, Anuj P.,Shaikh, Mohammedumar M.,Gurjar, Kamlesh K.,Chikhalia, Kishor H.
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p. 2049 - 2061
(2021/02/01)
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- 3-vinylquinolines as cancer cells inhibitors
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3-vinylquinolines analogs and methods of synthesizing the derivatives/analogs are provided. In particular, the compounds are useful for the treatment of cancer.
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- Discovery of novel quinoline-based analogues of combretastatin A-4 as tubulin polymerisation inhibitors with apoptosis inducing activity and potent anticancer effect
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A new series of quinoline derivatives of combretastatin A-4 have been designed, synthesised and demonstrated as tubulin polymerisation inhibitors. These novel compounds showed significant antiproliferative activities, among them, 12c exhibited the most potent inhibitory activity against different cancer cell lines (MCF-7, HL-60, HCT-116 and HeLa) with IC50 ranging from 0.010 to 0.042 μM, and with selectivity profile against MCF-10A non-cancer cells. Further mechanistic studies suggest that 12c can inhibit tubulin polymerisation and cell migration, leading to G2/M phase arrest. Besides, 12c induces apoptosis via a mitochondrial-dependant apoptosis pathway and caused reactive oxygen stress generation in MCF-7 cells. These results provide guidance for further rational development of potent tubulin polymerisation inhibitors for the treatment of cancer.Highlights A novel series of quinoline derivatives of combretastatin A-4 have been designed and synthesised. Compound 12c showed significant antiproliferative activities against different cancer cell lines. Compound 12c effectively inhibited tubulin polymerisation and competed with [3H] colchicine in binding to tubulin. Compound 12c arrested the cell cycle at G2/M phase, effectively inducing apoptosis and inhibition of cell migration.
- Ibrahim, Tarek S.,Hawwas, Mohamed M.,Malebari, Azizah M.,Taher, Ehab S.,Omar, Abdelsattar M.,Neamatallah, Thikryat,Abdel-Samii, Zakaria K.,Safo, Martin K.,Elshaier, Yaseen A. M. M.
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p. 802 - 818
(2021/03/29)
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- Synthesis of 2-(N-cyclicamino)quinoline combined with methyl (E)-3-(2/3/4-aminophenyl)acrylates as potential antiparasitic agents
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A rationally designed series of 2-(N-cyclicamino)quinolines coupled with methyl (E)-3-(2/3/4-aminophenyl)acrylates was synthesized and subjected to in vitro screening bioassays for potential antiplasmodial and antitrypanosomal activities against a chloroquine-sensitive (3D7) strain of Plasmodium falciparum and nagana Trypanosoma brucei brucei 427, respectively. Substituent effects on activity were evaluated; meta-acrylate 24 and the ortho-acrylate 29 exhibited the highest antiplasmodial (IC50 = 1.4 μM) and antitrypanosomal (IC50 = 10.4 μM) activities, respectively. The activity against HeLa cells showed that the synthesized analogs are not cytotoxic at the maximum tested concentration. The ADME (absorption, distribution, metabolism, and excretion) drug-like properties of the synthesized compounds were predicted through the SwissADME software.
- Bokosi, Fostino R. B.,Beteck, Richard M.,Laming, Dustin,Hoppe, Heinrich C.,Tshiwawa, Tendamudzimu,Khanye, Setshaba D.
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- Novel 1,2,4-triazine-quinoline hybrids: The privileged scaffolds as potent multi-target inhibitors of LPS-induced inflammatory response via dual COX-2 and 15-LOX inhibition
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Based on the observed pharmacophoric structural features for the reported dual COX/15-LOX inhibitors and inspired by the abundance of COX/LOX inhibitory activities reported for the 1,2,4-triazine and quinoline scaffolds, we designed and synthesized novel 1,2,4-triazine-quinoline hybrids (8a-n). The synthesized hybrids were evaluated in vitro as dual COXs/15-LOX inhibitors. The new triazine-quinoline hybrids (8a-n) exhibited potent COX-2 inhibitory profiles (IC50 = 0.047–0.32 μM, SI ~ 20.6–265.9) compared to celecoxib (IC50 = 0.045 μM, SI ~ 326). Moreover, they revealed potent inhibitory activities against 15-LOX enzyme compared to reference quercetin (IC50 = 1.81–3.60 vs. 3.34 μM). Hybrid 8e was the most potent and selective dual COX-2/15-LOX inhibitor (COX-2 IC50 = 0.047 μM, SI = 265.9, 15-LOX IC50 = 1.81 μM). These hybrids were further challenged by their ability to inhibit NO, ROS, TNF-α, IL-6 inflammatory mediators, and 15-LOX product, 15-HETE, production in LPS-activated RAW 264.7 macrophages cells. Compound 8e was the most potent hybrid in reducing ROS and 15-HETE levels showing IC50 values of 1.02 μM (11-fold more potent than that of celecoxib, IC50 = 11.75 μM) and 0.17 μM (about 43 times more potent than celecoxib, IC50 = 7.46 μM), respectively. Hybrid 8h exhibited an outstanding TNF-α inhibition with IC50 value of 0.40 μM which was about 25 times more potent than that of celecoxib and diclofenac (IC50 = 10.69 and 10.27 μM, respectively). Docking study of the synthesized hybrids into the active sites of COX-2 and 15-LOX enzymes ensures their favored binding affinity. To our knowledge, herein we reported the first 1,2,4-triazine-quinoline hybrids as dual COX/15-LOX inhibitors.
- Ghanim, Amany M.,Rezq, Samar,Ibrahim, Tarek S.,Romero, Damian G.,Kothayer, Hend
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- Hybrid quinoline-thiosemicarbazone therapeutics as a new treatment opportunity for Alzheimer’s disease-synthesis, in vitro cholinesterase inhibitory potential and computational modeling analysis
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Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia worldwide. The limited pharmacological approaches based on cholinesterase inhibitors only provide symptomatic relief to AD patients. Moreover, the adverse side effects such as nausea, vomiting, loss of appetite, muscle cramps, and headaches associated with these drugs and numerous clinical trial failures present substantial limitations on the use of medications and call for a detailed insight of disease heterogeneity and development of preventive and multifactorial therapeutic strategies on urgent basis. In this context, we herein report a series of quinoline-thiosemicarbazone hybrid therapeutics as selective and potent inhibitors of cholinesterases. A facile multistep synthetic approach was utilized to generate target structures bearing multiple sites for chemical modifications and establishing drug-receptor interactions. The structures of all the synthesized compounds were fully established using readily available spectroscopic techniques (FTIR, 1H- and 13C-NMR). In vitro inhibitory results revealed compound 5b as a promising and lead inhibitor with an IC50 value of 0.12 ± 0.02 μM, a 5-fold higher potency than standard drug (galantamine; IC50 = 0.62 ± 0.01 μM). The synergistic effect of electron-rich (methoxy) group and ethylmorpholine moiety in quinolinethiosemicarbazone conjugates contributes significantly in improving the inhibition level. Molecular docking analysis revealed various vital interactions of potent compounds with amino acid residues and reinforced the in vitro results. Kinetics experiments revealed the competitive mode of inhibition while ADME properties favored the translation of identified inhibitors into safe and promising drug candidates for pre-clinical testing. Collectively, inhibitory activity data and results from key physicochemical properties merit further research to ensure the design and development of safe and high-quality drug candidates for Alzheimer’s disease.
- Alsaab, Hashem O.,Aqsa, Sehar,Asif, Tahira Tasneem,Ibrar, Aliya,Kausar, Naghmana,Khan, Imtiaz,Munir, Rubina,Shahid, Noorma,Younas, Muhammad Tayyab,Zaib, Sumera
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- Design, Synthesis, and Antifungal Evaluation of Luotonin A Derivatives against Phytopathogenic Fungi
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Crop diseases caused by fungi threaten food security and exacerbate the food crisis. Inspired by the application of fungicide candidates from natural products in agrochemical discovery, a series of luotonin A derivatives were designed, synthesized, and evaluated for their antifungal activities against five plant fungi. Most of these compounds exhibited significant fungicidal activity against Botrytis cinerea in vitro with EC50 values less than 1 μg/mL. Among them, compounds w7, w8, w12, and w15 showed superior antifungal activity against B. cinerea with EC50 values of 0.036, 0.050, 0.042, and 0.048 μg/mL, respectively, which were more potent than boscalid (EC50 = 1.790 μg/mL). Preliminary mechanism studies revealed that compound w7 might pursue its antifungal activity by disrupting the fungal cell membrane and cell wall. Moreover, in vivo bioassay also indicated that compound w7 could be effective for the control of B. cinerea. The above results evidenced the potential of luotonin A derivatives as novel and promising candidate fungicides.
- Chu, Qing-Ru,Du, Sha-Sha,He, Ying-Hui,Li, Hai-Xing,Liu, Ying-Qian,Tang, Chen,Wang, Jing-Ru,Wang, Ren-Xuan,Wu, Tian-Lin,Yang, Cheng-Jie,Zhang, Zhi-Jun
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p. 14467 - 14477
(2021/12/09)
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- Synthesis, antioxidant and anticholinesterase activities of novel quinoline-aminophosphonate derivatives
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A series of 20 novel α-aminophosphonate derivatives bearing quinoline or quinolone moiety was designed and synthesized via Kabachnik-Fields reaction in the presence of triethylammonium acetate as a solvent and catalyst under ultrasound irradiation. This procedure affords products in high yields and short reaction times. Molecular structures of the synthesized compounds 4a-g and 5a-m were confirmed using various spectroscopic methods. The antioxidant activity of these compounds was evaluated by eight complementary in vitro tests. The anticholinesterase activity (AChE, BChE) of these compounds were also evaluated. In addition, theoretical calculations of all compounds were investigated as corrosion inhibitors using density functional theory (DFT). The results revealed that 16 of these compounds exhibited high levels of antioxidant activities depending on the assay and that most compounds showed more potent inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE).
- Bazine, Ismahene,Bensegueni, Rafik,Bensouici, Chawki,Boukhari, Abbes,Cheraiet, Zinelaabidine
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- Docking studies, antitumor and antioxidant evaluation of newly synthesized porphyrin and metalloporphyrin derivatives
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In this work, we have synthesized a series of novel porphyrin derivatives, 1–5, in high yields. The metal complexes of two of the newly synthesized porphyrin derivatives, 1a–d and 2a–d, have also been synthesized in high yields and characterized. In the synthesis of the new porphyrins and metalloporphrins, we employed our reported strategy in which we utilized N,N-dimethylformamide (DMF) as a capping agent in the reaction of pyrrole with different hetero-aryl aldehydes. The new porphyrin derivatives are equipped with different aromatic substituents and hetero-cycles at the peripheral position. The structures of the new compounds were confirmed by elemental and spectral analyses. The geometry and magnetic properties of the new metalloporphyrins 1a–d and 2a–d have also been studied. Antioxidant and cytotoxic activities of the new compounds were evaluated and structure-activity relationships were performed. Porphyrin derivatives 2a and 4 showed exceptional antioxidant activity compared to ascorbic acid as a reference. While the derivatives 2, 3, and 5 exhibited very strong cytotoxic activity against two human cell lines, HePG-2 and MCF-7. Docking for the most promising antioxidant porphyrins, 2a and 4, into the binding active site of antioxidant protein Human Peroxiredoxin (code: 1HD2) has been carried out to detect the degree of recognition antioxidant activity. Molecular docking of the most cytotoxic active porphyrins, 3 and 5, into the biding site of telomerase inhibitor enzyme has been carried out to assess the degree of recognition cytotoxic activity.
- Abou-Zeid, Laila,Ahmed, Asmaa,El-Asmy, Hala A.,Fadda, Ahmed A.,Omar, Walaa A. E.
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- Synthesis and molecular docking studies of quinoline derivatives as HIV non-nucleoside reverse transcriptase inhibitors
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Quinoline moiety is an important scaffold in the field of drug discovery and drug development, with a wide range of pharmacological activities. Quinoline derivatives are potent inhibitors for reverse transcriptase, which is responsible for the conversion of single-stranded viral RNA into double-stranded viral DNA.In the present study, we have designed and synthesized 2 series, namely pyrazoline and pyrimidine containing quinoline derivatives as non nucleoside reverse transcriptase inhibitors (NNRTIs). Eleven compounds were synthesized and characterized by 1H and 13C NMR and mass spectrophotometry. The synthesized compounds were also docked on an HIV reverse transcriptase binding site (PDB: 4I2P); most of these compounds showed good binding interactions with the active domain of the receptor. Most of the compounds displayed a docking score higher than those of standard drugs. Among the synthesized quinoline derivatives, compound 4 exhibited the highest docking score (-10.675).
- Bhardwaj, Nivedita,Choudhary, Diksha,Pathania, Akashdeep,Baranwal, Somesh,Kumar, Pradeep
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p. 1623 - 1641
(2021/01/05)
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- Synthesis of 2-methoxy-3-(thiophen-2-ylmethyl)quinoline containing amino carbinols as antitubercular agents
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We have designed and synthesized 2-methoxy-3-(thiophen-2-ylmethyl)quinoline containing amino carbinols as possible anti-tubercular agents to combat the disease. These molecules were synthesized by tethering amino ether linkage with hydroxyl group to diarylquinoline skeleton; hydroxyl and amine chains were engrafted on diaryl ring. They were evaluated against strain (H37Ra) of Mycobacterium tuberculosis and most of compounds showed in vitro antitubercular activity. Two compounds having diaryl quinoline hydroxyl amino ether scaffold and three compounds having diaryl amino alkyl carbinol core showed activities at 6.25 μg/mL. This study explores diaryl carbinol prototype as inhibitor against Mycobacterium tuberculosis.
- Karkara, Bidhu Bhusan,Mishra, Shashank Shekhar,Panda, Gautam,Singh, Bhupendra N.
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- Synthesis and characterization of mesoporous organosilica supported palladium (SBA-Pr-NCQ-Pd) as an efficient nanocatalyst in the Mizoroki–Heck coupling reaction
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In the present study, the modification of a mesoporous organosilica nanocomposite SBA-15 (Santa Barbara Amorphous 15) was carried out in two steps, first through the surface functionalization of SBA-Pr-NH2 with 2-chloroquinoline-3-carbaldehyde to form SBA-Pr-NCQ, and then through a post-modification process with palladium ions. The target nanocompound structure of SBA-Pr-NCQ-Pd was characterized by different techniques (thermogravimetric analysis, X-ray diffraction, scanning electron microscopy, Energy-dispersive X-ray spectroscopy (EDX), and Fourier transform infrared spectroscopy). The catalytic performance of the porous inorganic–organic hybrid nanocomposite (SBA-Pr-NCQ-Pd) in one of the most important carbon–carbon bond-forming processes, the Mizoroki–Heck coupling reaction of aryl halides and methacrylate in water/ethanol media, was examined. Compared to previous reports, this protocol afforded some advantages, such as high yields of products, short reaction times, catalyst stability without leaching, simple methodology, easy workup, and greener conditions. Also, the nanocatalyst can be easily separated from the reaction mixture and reused several times without a significant decrease in activity and promises economic as well as environmental benefits.
- Moradi, Razieh,Mohammadi Ziarani, Ghodsi,Badiei, Alireza,Mohajer, Fatemeh
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- Synthesis and photophysical investigation of AIEgen dyes bearing quinoline and BODIPY scaffolds
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[Figure not available: see fulltext.] Quinoline-based BODIPY AIEgen dyes were synthesized and the structures were elucidated by 1H, 13C, 19F NMR, FT-IR spectroscopy and mass spectrometry methods. Their photophysical proper
- ?i?man, ?lkay,Arslan, Bar?? Se?kin,Derin, Yavuz,M?s?r, Bü?ra Albayrak,Nebio?lu, Mehmet,Tutar, Ahmet
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p. 1542 - 1547
(2021/01/11)
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- Synthesis biological studies of some new heterocyclic compound derived from 2-chloro-3-formyl quinoline and 4-(benzyl sulfonyl) acetophenone
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A new series of quinoline chalcones have been prepared from condensations of 2-chloro-3-formyl quinoline (1) with 4-(benzothio) acetophenone(2) and 4-(benzyl sulfonyl) acetophenone(3). The reaction of chalcones(4,5)with bromine gives dibromide(6,7). New pyrazoline derivatives were synthesized by condensation of chalcones (4 or 5) with hydrazine hydrate to give (8,9) and with hydrazine hydrate in glacial acetic acid(gla) to give (10,11) and with phenyl hydrazine to give (12,13). The prepared chalcones (4,5) and dibromide(6,7) and pyrazoline derivative (8-13)have been screened for antibacterial activities against two gram positive staphylococcus aureus and staphylococcus epidermidis and two gram negative Escherichia coli and Proteus vulgaris. The synthesized compounds are proven by IR & NMR spectral and physical method.
- Saleh, Mohanad Y.,Ayoub, Ala I.,Hammady, Ali Obaid
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p. 4769 - 4776
(2020/12/25)
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- AMINO ACID DERIVATIVES FOR THE TREATMENT OF INFLAMMATORY DISEASES
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The present disclosure provides certain amino acid derivatives that inhibit NF-kB activation and are therefore useful for the treatment of inflammatory diseases. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.
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Page/Page column 58-59
(2020/08/13)
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- Synthesis and Antibacterial, Antioxidant, and Molecular Docking Analysis of Some Novel Quinoline Derivatives
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2-Chloroquinoline-3-carbaldehyde and 2-chloro-8-methylquinoline-3-carbaldehyde derivatives were synthesized through Vilsmeier formulation of acetanilide and N-(o-tolyl)acetamide. Aromatic nucleophilic substitution reaction was used to introduce various nucleophiles in place of chlorine under different reaction conditions. The carbaldehyde group was oxidized by permanganate method and reduced with metallic sodium in methanol and ethanol. The synthesized compounds were characterized by UV-Vis, IR, and NMR. The antibacterial activity of the synthesized compounds was screened against two Gram-positive bacteria (Bacillus subtilis ATCC6633 and Staphylococcus aureus ATCC25923) and two Gram-negative bacteria (Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853). Most of the compounds displayed potent activity against two or more bacterial strains. Among them, compounds 6 and 15 showed maximum activity against Pseudomonas aeruginosa with mean inhibition zones of 9.67 ± 1.11 and 10.00 ± 0.44 mm, respectively, while ciprofloxacin showed mean inhibition zone of 8.33 ± 0.44 mm at similar concentration. On the other hand, compound 8 exhibited maximum activity against Escherichia coli with inhibition zones of about 9.00 ± 0.55 mm at 300 μg/mL and 11.33 ± 1.11 mm at 500 μg/mL. The radical scavenging activity of these compounds was evaluated using 1,1-diphenyl-2-picryl hydrazyl (DPPH), and all of them displayed moderate antioxidant activity, with compound 7 exhibiting the strongest activity. The molecular docking study of the synthesized compounds was conducted to investigate their binding pattern with DNA gyrase, all of them were found to have minimum binding energy ranging from -6.0 to -7.33 kcal/mol, and the best result was achieved with compound 11. The findings of the in vitro antibacterial and molecular docking analysis demonstrated that the synthesized compounds have potential of antibacterial activity and can be further optimized to serve as lead compounds.
- Belay, Zerihun,Eswaramoorthy, Rajalakshmanan,Melaku, Yadessa,Zeleke, Digafie
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- Design, synthesis and biological evaluation of novel 5-((substituted quinolin-3-yl/1-naphthyl) methylene)-3-substituted imidazolidin-2,4-dione as HIV-1 fusion inhibitors
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A series of novel 5-(substituted quinolin-3-yl or 1-naphthyl)methylene)-3-substituted imidazolidin-2,4-dione 9–26 was designed and synthesized. The prepared compounds were identified using 1H NMR, 13C NMR as well as elemental analyses. The inhibitory activity of 9–26 on HIV-1IIIB replication in MT-2 cells was evaluated. Some derivatives showed good to excellent anti-HIV activities as compounds 13, 18, 19, 20, 22 and 23. They showed EC50 of 0.148, 0.460, 0.332, 0.50, 0.271 and 0.420 μM respectively being more potent than compound I (EC50 = 0.70 μM) and II ( EC50 = 2.40 μM) as standards. The inhibitory activity of 9–26 on infected primary HIV-1 domain, 92US657 (clade B, R5) was investigated. All the tested compounds consistently inhibited infection of this virus with EC50 from 0.520 to 11.857 μM. Results from SAR studies showed that substitution on ring A with 6/7/8-methyl group resulted in significant increase in the inhibitory activity against HIV-1IIIB infection (5- >300 times) compared to the unsubstituted analog 9. The cytotoxicity of these compounds on MT-2 cells was tested and their CC50 values ranged from 11 to 85 μM with selectivity indexes ranged from 0.53 to 166. The docking study revealed nice fitting of the new compounds into the hydrophobic pocket of HIV-1 gp41 and higher affinity than NB-64. Compound 13, the most active in preventing HIV-1IIIB infection, adopted a similar orientation to compound IV. Molecular docking analysis of the new compounds revealed hydrogen bonding interactions between the imidazolidine-2,4-dione ring and LYS574 which were missed in the weakly active derivatives.
- AL-Mahmoudy, Amany M. M.,Abdel-Aal, Eatedal H.,AlAwadh, Mohammed A.,Alhakamy, Nabil A.,Asfour, Hany Z.,Bokhtia, Riham M.,Elagawany, Mohamed,Gouda, Ahmed M.,Ibrahim, Tarek S.,Panda, Siva,Taher, Ehab S.,Youssif, Bahaa G. M.
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- Synthesis, structural elucidation, intramolecular hydrogen bonding and DFT studies of quinoline-chalcone-chromene hybrids
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Eight hydroxyquinoline-chromene chalcones, of which six were new, were synthesized using the Vilsmeier-Haack reaction and Claisen-Schmidt condensation. These contain either mono or dichromene functionality. The hydroxyl proton chemical shift of both types of compounds at varying temperature indicated weakened hydrogen bonds with an increase in temperature, however there was no significant difference to the slopes of the OH chemical shift curves (3.4 x10-3 for the 2-methoxychromene derivative and 3.1 x10-3 for the 6-methoxydichromene derivative. Potential energy scans of these two compounds were obtained using B3LYP/6-311 G level theory in the gas phase, and showed the enol form to be most stable for both molecules and that the energy barrier to make proton transfer possible is 5.076 and 3.989 Kcal mol-1 for the 2-methoxychromene and 6-methoxydichromene derivatives respectively.
- Thungatha, Lamla,Alapour, Saba,Koorbanally, Neil A.
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- Design and synthesis of novel pyrazolo[3,4-d]pyrimidin-4-one bearing quinoline scaffold as potent dual PDE5 inhibitors and apoptotic inducers for cancer therapy
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PDE5 targeting represents a new and promising strategy for apoptosis induction and inhibition of tumor cell growth due to its over-expression in diverse types of human carcinomas. Accordingly, we report the synthesis of series of pyrazolo[3,4-d]pyrimidin-4-one carrying quinoline moiety (11a-r) with potential dual PDE5 inhibition and apoptotic induction for cancer treatment. These hybrids were structurally elucidated and characterized with variant spectroscopic techniques as 1H NMR, 13C NMR and elemental analysis. The assessment of their anticancer activities has been declared. All the rationalized compounds 11a-r have been selected for their cytotoxic activity screening by NCI against 60 cell lines. Compounds 11a, 11b, 11j and 11k were the most active hybrids. Among all, compound 11j was further selected for five dose tesing and it displayed outstanding activity with strong antitumor activity against the nine tumor subpanels tested with selectivity ratios ranging from 0.019 to 8.3 at the GI50 level. Further, the most active targets 11a, b, j and k were screened for their PDE5 inhibitory activity, compound 11j (with IC50 1.57 nM) exhibited the most potent PDE5 inhibitory activity. Moreover, compound 11j is also showed moderate EGFR inhibition with IC50 of 5.827 ± 0.46 μM, but significantly inhibited the Wnt/β-catenin pathway with IC501286.96 ± 12.37 ng/mL. In addition, compound 11j induced the intrinsic apoptotic mitochondrial pathway in HepG2 cells as evidenced by the lower expression levels of the anti-apoptotic Bcl-2 protein, and the higher expression of the pro-apoptotic protein Bax, p53, cytochrome c and the up-regulated active caspase-9 and caspase-3 levels. All results confirmed by western blotting assay. Compound 11j exhibit pre G1 apoptosis and cell cycle arrest at G2/M phase. In conclusion, hybridization of quinoline moiety with the privileged pyrazolo[3,4-d]pyrimidinon-4-one structure resulted in highly potent anticancer agent, 11j, which deserves more study, in particular, in vivo and clinical investiagtions, and it is expected that these results would be applied for more drug discovery process.
- Ibrahim, Tarek S.,Hawwas, Mohamed M.,Taher, Ehab S.,Alhakamy, Nabil A.,Alfaleh, Mohamed A.,Elagawany, Mohamed,Elgendy, Bahaa,Zayed, Gamal M.,Mohamed, Mamdouh F.A.,Abdel-Samii, Zakaria K.,Elshaier, Yaseen A.M.M.
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- Potent quinoline-containing combretastatin a-4 analogues: Design, synthesis, antiproliferative, and anti-tubulin activity
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A novel series of quinoline derivatives of combretastatin A-4 incorporating rigid hydrazone and a cyclic oxadiazole linkers were synthesized and have demonstrated potent tubulin polymerization inhibitory properties. Many of these novel derivatives have shown significant antiproliferative activities in the submicromolar range. The most potent compound, 19h, demonstrated superior IC50 values ranging from 0.02 to 0.04 μM against four cancer cell lines while maintaining low cytotoxicity in MCF-10A non-cancer cells, thereby suggesting 19h’s selectivity towards proliferating cancer cells. In addition to tubulin polymerization inhibition, 19h caused cell cycle arrest in MCF-7 cells at the G2/M phase and induced apoptosis. Collectively, these findings indicate that 19h holds potential for further investigation as a potent chemotherapeutic agent targeting tubulin.
- Ibrahim, Tarek S.,Hawwas, Mohamed M.,Malebari, Azizah M.,Taher, Ehab S.,Omar, Abdelsattar M.,O’boyle, Niamh M.,McLoughlin, Eavan,Abdel-Samii, Zakaria K.,Elshaier, Yaseen A. M. M.
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- A cyano dihydroisoquinolines IDO1 inhibitors, preparation method and application thereof
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The invention relates to a cyano dihydroisoquinolines IDO1 inhibitors, preparation method and application thereof, cyano dihydroisoquinolines IDO1 inhibitors of the general formula I is compound or its pharmaceutically acceptable salt. Preparation method
- -
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Paragraph 0053-0056
(2019/03/31)
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- Design, Synthesis and Anticancer Evaluation of New Substituted Thiophene-Quinoline Derivatives
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A series of new isoxazolyl, triazolyl and phenyl based 3-thiophen-2-yl-quinoline derivatives were synthesized adopting click chemistry approach. In addition, the synthesis of new useful synthon, (2-chloroquinolin-3-yl) (thiophen-2-yl) methanol, is reported. The obtained compounds were characterized by spectral data analysis and evaluated for their anticancer activity. All the derivatives were subjected to in vitro MTT cytotoxicity screening assay against a panel of four different human cancer cell lines, liver (HepG-2), colon (HCT-116), human cervical cancer (HeLa) and breast (MCF-7). Out of a library of 17 compounds, two compounds have been identified as potent and selective cytotoxic agents against HeLa and MCF-7 cell lines. SAR studies for such hybridized analogues were investigated and phenyl derivatives were proved to be more potent than isoxazole and triazole derivatives. Furthermore, the promising compounds were selected for in vitro inhibition of EGFR-TK and Topo II enzymes. Also, they were subjected to cell cycle arrest analysis and apoptosis assay on MCF-7 cells. Our recent finding highlights these thiophene-quinoline analogues as a promising class of compounds for further studies concerning new anticancer therapies.
- Othman, Dina I.A.,Selim, Khalid B.,El-Sayed, Magda A.-A.,Tantawy, Atif S.,Amen, Yhiya,Shimizu, Kuniyoshi,Okauchi, Tatsuo,Kitamura, Mitsuru
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- CRBN LIGANDS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of CRBN, and the treatment of CRBN-mediated disorders.
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-
Paragraph 00544-00546
(2019/08/20)
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- FLUORESCENT DYE AGENT AND CARBOSTYRIL COMPOUND
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PROBLEM TO BE SOLVED: To provide a novel fluorescent dye agent. SOLUTION: A fluorescent dye agent contains a carbostyril compound represented by formula (1) [in the formula (1), R1 is H, a halogen atom, a hydroxyl group, a cyano group, a nitro group or the like; R2 is O; R3 is a halogen atom, a carboxyl group, an ester group, an amide group or the like; R4-R6 and R8 independently represent H, a halogen atom, a nitro group, a cyano group or the like, where mutually adjacent groups of R4-R8 may be bound to form a ring; R7 is H, a substituted or unsubstituted aliphatic group or the like]. SELECTED DRAWING: None COPYRIGHT: (C)2019,JPOandINPIT
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-
Paragraph 0149; 0150
(2019/04/03)
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- Catalyst-free assembly of giant tris(heteroaryl)methanes: Synthesis of novel pharmacophoric triads and model sterically crowded tris(heteroaryl/aryl)methyl cation salts
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A series of giant tris(heteroaryl)methanes are easily assembled by one-pot three-component synthesis by simple reflux in ethanol without catalyst or additives. Diversely substituted indoles (Ar1) react with quinoline aldehydes, quinolone aldehydes, chromone aldehydes, and fluorene aldehydes (Ar2CHO) and coumarins (Ar3) in 1:1:1 ratio to form the corresponding tris(heteroaryl)methanes (Ar1Ar2Ar3)CH along with (Ar1Ar1Ar2)CH triads. A series of new 2:1 triads were also synthesized by coupling substituted indoles with Ar2CHO. The coupling reactions could also be carried out in water (at circa 80 °C) but with chemoselectivity favoring (Ar1Ar1Ar2)CH(Ar1Ar2Ar3)CH. The molecular structure of a representative (Ar1Ar2Ar3)CH triad was confirmed by X-ray analysis. Model tris(heteroaryl/aryl)methylium salts were generated by reaction with DDQ/HPF6 and studied by NMR and by DFT and GIAO-DFT.
- Abonia, Rodrigo,Gutiérrez, Luisa F.,Insuasty, Braulio,Quiroga, Jairo,Laali, Kenneth K.,Zhao, Chunqing,Borosky, Gabriela L.,Horwitz, Samantha M.,Bunge, Scott D.
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p. 642 - 654
(2019/04/17)
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- One-pot synthesis of quinoline-fused [1,4]thiazepines via the tandem Ugi/post-Ugi reactions
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A one-pot strategy has been developed for the synthesis of novel tetrahydro-[1,4]thiazepino[7,6-b]quinoline-5-carboxamide derivatives. These reactions presumably proceed by the combination of a Ugi 4CR and three intramolecular SN2 aliphatic, an alkaline hydrolysis and an intramolecular cyclization SNAr nucleophilic substitution processes in moderate to good yields. Unambiguous assignment of the molecular structures was carried out by single-crystal X-ray diffraction.
- Ghandi, Mehdi,Efteghar, Irene,Abbasi, Alireza
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p. 325 - 332
(2019/01/28)
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- Synthesis, antibacterial activity and docking studies of substituted quinolone thiosemicarbazones
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Fifteen 2-quinolone thiosemicarbazone derivatives of which eleven were new, were synthesized at room temperature. The key intermediate was the quinolone carbaldehyde, from which thiosemicarbazones were formed by the reaction of thiosemicarbazides with the aldehyde moiety. The structures of the synthesized compounds were elucidated by 1D and 2D-NMR spectroscopy and mass spectrometry. The synthesized compounds showed antibacterial activity with MBCs in the range 0.80 to 36.49 mM against Staphylococcus aureus, Staphylococcus aureus Rosenbach (MRSA), Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli and Salmonella typhimurium. The best activity was seen when a larger halogen such as chlorine and bromine were substituted at C-6 on the quinolone scaffold and when a planar phenyl group was present on the thiosemicarbazone moiety. Activity was reduced when a smaller fluorine atom was present at C-6 or when a methyl group was attached to the thiosemicarbazone. This group of compounds showed a high negative binding affinity, which suggested promising antimcrobial activity. The 6-chloro derivative with a phenyl group on the thiosemicarbazone had the greatest negative binding affinity.
- Govender, Hogantharanni,Mocktar, Chunderika,Kumalo, Hezekiel M.,Koorbanally, Neil A.
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p. 1074 - 1081
(2019/06/10)
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- Antimicrobial activity of quinoline-based hydroxyimidazolium hybrids
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Eight quinoline-based hydroxyimidazolium hybrids 7a-h were prepared and evaluated in vitro against a panel of clinically important fungal and bacterial pathogens, including mycobacteria. Hybrid compounds 7c-d showed remarkable antifungal activity against Cryptococcus neoformans with a minimum inhibitory concentration (MIC) value of 15.6 μg/mL. Against other opportunistic fungi such as Candida spp. and Aspergillus spp., these hybrids showed MIC values of 62.5 μg/mL. Regarding their antibacterial activity, all the synthetic hybrids demonstrated little inhibition of Gram-negative bacteria (MIC ≥50 μg/mL), however, hybrid 7b displayed >50% inhibition against Klebsiella pneumoniae at 20 μg/mL and full inhibition at 50 μg/mL. Moreover, this hybrid was shown to be a potent anti-staphylococcal molecule, with a MIC value of 2 μg/mL (5 μM). In addition, hybrid 7h also demonstrated inhibition of Staphylococcus aureus at 20 μg/mL (47 μM). Hybrids 7a and 7b were the most potent against Mycobacterium tuberculosis H37Rv with MIC values of 20 and 10 μg/mL (46 and 24 μM), respectively. The 7b hybrid demonstrated high selectivity in killing S. aureus and M. tuberculosis H37Rv in comparison with mammalian cells (SI >20), and thus it can be considered a hit molecule for mechanism of action studies and the exploration of related chemical space.
- Abonia, Rodrigo,Bernal, Anthony,Guzman, Juan,Insuasty, Braulio,Insuasty, Daniel,Marquez, Edgar,Puerto, Gloria,Quiroga, Jairo,Svetaz, Laura,Vidal, Oscar,Zacchino, Susana
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- Coupling-Isomerization-Cycloisomerization Reaction (CICIR) – An Unexpected and Efficient Domino Approach to Luminescent 2-(Hydroxymethylene)indenones
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A Pd/Cu-catalyzed base mediated domino process of ortho-halo (hetero)aryl carboxaldehydes and propargyl alcohols unexpectedly furnish 2-(hydroxymethylene)indenones in good to excellent yield as a result of a coupling-isomerization-cycloisomerization reaction (CICIR). In addition, the title compounds constitute an interesting class of luminophores with tunable emission solvatochromicity.
- Ghazvini, Helya Janatian,Armaghan, Mahsa,Janiak, Christoph,Balalaie, Saeed,Müller, Thomas J. J.
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supporting information
p. 7058 - 7062
(2019/11/11)
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- Synthesis of C-2 and C-3 substituted quinolines and their evaluation as anti-HIV-1 agents
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A plenty of natural products and synthetic derivatives containing quinoline moiety have been reported to possess various pharmacological activities. Quinolines such as 2-styrylquinolines and 8-hydroxyquinolines are extensively studied for their anti-HIV-1
- Shah, Purvi,Naik, Dharav,Jariwala, Nisha,Bhadane, Deepali,Kumar, Sanjay,Kulkarni, Smita,Bhutani, Kamlesh Kumar,Singh, Inder Pal
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p. 591 - 601
(2018/07/29)
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- Tandem and transition metal-free synthesis of novel benzoimidazo-quinazoline as highly selective Hg2+ sensors
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A one-pot procedure for the synthesis of novel planar aza-heterocycles possessing good fluorescence potencies was described. These benzo-imidazopyrimido[4,5-b]quinolone derivatives came from the reaction of 2-chloroquinoline-3-carboxaldehydes and 2-aminobenzimidazole using K2CO3 in DMF. The fluorescence study of these conjugated systems was also considered, which revealed that they have highly selective sensing of mercury. Consequently, to investigate another aspect of the reaction, a three-component reaction was developed by adding malononitrile to the aforementioned starting materials in the presence of l-proline under reflux condition in H2O/EtOH to provide amino-quinolin-3-yl-dihydrobenzo-imidazo-pyrimidine-3-carbonitriles in good yields.
- Shiri, Morteza,Heravi, Majid M.,Faghihi, Zeinab,Zadsirjan, Vahideh,Mohammadnejad, Masoumeh,Ranjbar, Maryam
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p. 2439 - 2449
(2018/01/01)
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- Design, synthesis and pharmacological evaluation of novel 2-chloro-3-(1: H -benzo [d] imidazol-2-yl)quinoline derivatives as antitumor agents: In vitro and in vivo antitumor activity, cell cycle arrest and apoptotic response
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A series of novel 2-chloro-3-(1H-benzo[d]imidazol-2-yl)quinoline derivatives (3a1-3d6) were designed and synthesized as antitumor agents. In vitro antitumor assay results showed that some compounds exhibited moderate to high inhibitory activities against HepG2, SK-OV-3, NCI-H460 and BEL-7404 tumor cell lines, and most compounds exhibited much lower cytotoxicities against HL-7702 normal cell line compared to 5-FU and cisplatin. In vivo antitumor assay results showed that the representative compound 3a1 exhibited effective inhibition on tumor growth in the HepG2 xenograft mouse model. Mechanistic studies suggested that 3a1 may exert antitumor activity by the up-regulation of Bax, intracellular Ca2+ release, ROS generation, p21, p27 and p53, downregulation of Bcl-2, activation of caspase-9 and caspase-3 and subsequent cleavage of PARP, and inhibition of CDK activity.
- Kuang, Wen-Bin,Huang, Ri-Zhen,Fang, Yi-Lin,Liang, Gui-Bin,Yang, Chen-Hui,Ma, Xian-Li,Zhang, Ye
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p. 24376 - 24385
(2018/07/25)
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- Synthesis and Bioactivity of Quinoline-3-carboxamide Derivatives
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Twelve novel substituted 2-chloroquinoline-3-carboxamide derivatives were prepared from acetanilides using the Vilsmeier–Haack reaction, producing 2-chloro-3-carbaldehyde quinolines, followed by oxidation of the 3-carbaldehyde to the carboxylic acid and coupling this group with various anilines. The structures of the synthesized compounds were confirmed by NMR, mass spectrometry, and single crystal X-ray diffraction. The chemical shifts of H-5 and H-8 were shown to be influenced by the substituent at C-6. The substituent at C-6 was also seen to affect the chemical shift of C-5, C-7, and C-8, with C-5 and C-7 being more shielded in 5j (F substituted) in comparison with 5g (Cl substituted) and 5d (CH3 substituted). The compounds showed weak activity in the mM range against Gram-positive and Gram-negative bacteria of which 5b, 5d, and 5f showed the best activity with minimum bactericidal concentration values for 5b being 3.79?mM against methicillin-resistant Staphylococcus aureus and 5d and 5f having minimum bactericidal concentration values of 3.77 and 1.79?mM against S.?aureus ATCC 25923, respectively.
- Govender, Hogantharanni,Mocktar, Chunderika,Koorbanally, Neil A.
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p. 1002 - 1009
(2018/02/15)
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- Synthesis, antiplasmodial and antitrypanosomal evaluation of a series of novel 2-oxoquinoline-based thiosemicarbazone derivatives
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Herein a series of novel thiosemicarbazones (TSCs) derived from 2-oxoquinoline scaffold is reported, and the target compounds have been successfully synthesized and characterized using standard spectroscopic techniques. The in vitro biological activities of synthesized molecules were evaluated against Plasmodium falciparum malaria parasites (strain 3D7), Trypanosoma brucei brucei parasites (strain 427) and HeLa cells. All the compounds displayed modest or no activity at a concentration of 20 μM and percentage viability of >50 % was often observed. Except for compound 9o, none of the final compounds exhibited cytotoxic effects against HeLa cells at 20 μM.
- Darrell, Oliver T.,Hulushe, Siyabonga T.,Mtshare, Thanduxolo E.,Beteck, Richard M.,Isaacs, Michelle,Laming, Dustin,Hoppe, Heinrich C.,Krause, Rui W.M.,Khanye, Setshaba D.
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p. 174 - 181
(2019/01/04)
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- Preparation method of 2-chloro-3-formyl quinoline derivatives
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The invention relates to a preparation method of 2-chloro-3-formyl quinoline derivatives. The preparation method comprises the following steps: by taking acetanilide or substituted acetanilide as a raw material, reacting with bis(trichloromethyl) carbonate (BTC) and N,N-dimethylformamide (DMF) in an organic solvent to obtain a target compound. The preparation method provided by the invention has the advantages that bis(trichloromethyl) carbonate is adopted for replacing a phosphorus-containing or sulfur-containing chlorination reagent, so that the problems of treatment of phosphorus-containing or sulfur-containing byproducts and wastewater discharge in a production process are solved, the preparation method has the characteristics that raw materials are easily available, the cost is low, operation steps are simple, reaction conditions are mild, the energy consumption is low, the reaction process is safe, the environmental pollution is small and the clean production can be realized, and the preparation method has industrialization application prospect.
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Paragraph 0005; 0022-0033
(2017/07/19)
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- QUINOLONE CHALCONE COMPOUNDS AND USES THEREOF
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The present disclosure relates to novel compounds, compositions comprising these compounds, and their use, for example for the treatment of cancer. In particular, the present disclosure includes compounds of Formula (I), and compositions and uses thereof.
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Paragraph 00117; 00119; 00122
(2017/07/14)
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- Synthesis of indolizinoquinolinones through three- and four-component domino Knoevenagel / hetero-Diels–Alder reactions: novel access to (+)-camptothecin
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[Figure not available: see fulltext.] The fused heterocyclic indolizinoquinolinone system is a key structural feature of several highly bioactive alkaloids, including camptothecin. Camptothecin has been efficiently obtained by a three- or four-component domino Knoevenagel / hetero-Diels–Alder reaction of aldehyde, Meldrum's acid, and enol ether in the presence or absence of alcohol, followed by reductive cleavage of the amine protecting group. The obtained products were further transformed along several different routes leading to camptothecin.
- Tietze, Lutz F.,Bischoff, Matthias,Khan, Taukeer A.,Liu, Deshan
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p. 434 - 445
(2017/07/07)
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- Synthesis and anticonvulsant activity of a combined pharmacophore of 2-oxo-1,2-dihydroquinoline containing 1,3,4-oxadiazole derivatives
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The significance of 1,3,4-oxadiazolo-quinoline as pharmacophore in the discovery of better antiepileptic agent led to the exploration of the synthesis of new series of 3-[5-(naphthyloxymethyl/naphthyl-methyl/2-phenoxymethyl) benzoimidazol-1-ylmethyl)-[1,3
- Salahuddin,Mazumder, Avijit,Yar, Mohammad Shahar,Sarafroz, Mohammad
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