- Anticancer Activity of Iridium(III) Complexes Based on a Pyrazole-Appended Quinoline-Based BODIPY
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A pyrazole-appended quinoline-based 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (L1, BODIPY) has been synthesized and used as a ligand for the preparation of iridium(III) complexes [Ir(phpy)2(L1)]PF6 (1; phpy = 2-phenylpyridine) and [(η5-C5Me5)Ir(L1)Cl]PF6 (2). The ligand L1 and complexes 1 and 2 have been meticulously characterized by elemental analyses and spectral studies (IR, electrospray ionization mass spectrometry, 1H and 13C NMR, UV/vis, fluorescence) and their structures explicitly authenticated by single-crystal X-ray analyses. UV/vis, fluorescence, and circular dichroism studies showed that complexes strongly bind with calf-thymus DNA and bovine serum albumin. Molecular docking studies clearly illustrated binding through DNA minor grooves via van der Waals forces and their electrostatic interaction and occurrence in the hydrophobic cavity of protein (subdomain IIA). Cytotoxicity, morphological changes, and apoptosis have been explored by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Hoechst 33342 staining. IC50 values for complexes (1, 30 μM; 2, 50 μM) at 24 h toward the human cervical cancer cell line (HeLa) are as good as that of cisplatin (21.6 μM) under analogous conditions, and their ability to kill cancer cells lies in the order 1 > 2. Because of the inherent emissive nature of the BODIPY moiety, these are apt for intracellular visualization at low concentration and may find potential applications in cellular imaging and behave as a theranostic agent.
- Paitandi, Rajendra Prasad,Mukhopadhyay, Sujay,Singh, Roop Shikha,Sharma, Vinay,Mobin, Shaikh M.,Pandey, Daya Shankar
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- Fluorescence, DNA Interaction and Cytotoxicity Studies of 4,5-Dihydro-1H-Pyrazol-1-Yl Moiety Based Os(IV) Compounds: Synthesis, Characterization and Biological Evaluation
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Osmium(IV) pyrazole compounds and ligands were synthesized and well characterised. Ligands were characterized by heteronuclear NMR spectroscopy (1H & 13C), elemental analysis, IR spectroscopy and liquid crystal mass spectroscopy. Os(
- Pursuwani, Bharat H.,Bhatt, Bhupesh S.,Vaidya, Foram U.,Pathak, Chandramani,Patel, Mohan N.
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- Synthesis of novel probe 2-chloro-6-methoxy-3-phenyl hydrazone quinoline and its application to detection of persulphate in aqueous ethanol solution by fluorescence turn on
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Abstract: A highly sensitive and selective fluorimetric detection method has been developed for persulphate anion using fluorescence turn on of 2-chloro-6-methoxy-3-phenyl hydrazone quinoline (Cl-MPHQ) in aqueous ethanol solution. Cl-MPHQ is a weakly fluorescent compound synthesized via a one-step reaction of 2-chloro-6-methoxyquinoline-3-carboxyaldehyde (Cl-MQCA) and phenyl hydrazine. The treatment of Cl-MPHQ with persulphate ion in aqueous ethanol solution (1:1?V/V) generates fluorescent Cl-MQCA, through C=N bond cleavage. The fluorescence intensity increased linearly with the concentration of persulphate ion (0–100?μmol?L?1). The detection limit of the method is 1?μmol?L?1determined from the standard deviation of the blank signal (3σ). The relative standard deviation of the method is 3% for 20?μmol?L?1 of persulphate ion. The proposed method is simple, sensitive and useful for selective detection of persulphate ion in an aqueous ethanol solution. Graphical Abstract: [Figure not available: see fulltext.].
- Patil, Dhanshri V.,Patil, Vishal S.,Sankpal, Sandeep A.,Kolekar, Govind B.,Patil, Shivajirao R.
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- Morphological tuning via structural modulations in AIE luminogens with the minimum number of possible variables and their use in live cell imaging
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With intent to fine tune the morphological and photophysical properties, three novel AIE luminogens (BQ1-BQ3) based on quinoline-BODIPY have been synthesized. A judicious choice of substituents (-H, -CH3, -OCH3) in these systems led to nanoballs in BQ1 and BQ2, while in BQ3 it led to reticulated nanofibers with diverse photophysical behaviours. This journal is
- Singh, Roop Shikha,Gupta, Rakesh Kumar,Paitandi, Rajendra Prasad,Dubey, Mrigendra,Sharma, Gunjan,Koch, Biplob,Pandey, Daya Shankar
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- Synthesis, crystal structure, anticancer and molecular docking studies of quinolinone-thiazolidinone hybrid molecules
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A new series of quinolone-thiazolidinone hybrid molecules 8a-o were prepared. Quinoline compounds were synthesized by Meth-Cohn synthesis and were condensed with 2,3-disubstituted thiazolidinone. These molecules were screened for their anticancer activities against MDA-MB-231 and MCF-7 cell line using MTT assay. Potent compounds were tested for their cytotoxicity on normal HEK 293 cell lines and most potent compound was tested for its cell cycle analysis. Molecular docking and molecular dynamic studies were performed on human N-acetyl transferase (hNAT-1) protein using Schrodinger molecular docking toolkit. Compound 8n emerged as potent with IC50 8.16?μM against MDA-MB-231 cell line followed by 8e with IC50 17.68?μM. Compound 8n arrested cell cycle at G2/M phase and was non-toxic to human normal kidney cell line. The potent compound 8n binds well with human NAT-1 protein with remarkable hydrogen bonding and π–π interactions. Molecular dynamic studies of 8n further confirm the target for these molecules. Target quinolinone-thiazolidinones were found to be new class of compounds targeting hNAT-1 and can serve as new lead compounds in drug discovery.
- Kumar, Vasantha,Rai, Vaishali M.,Udupi, Vishwanatha,Shivalingegowda, Naveen,Pai, Vinitha R.,Krishnappagowda, Lokanath Neratur,Poojary, Boja
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p. 793 - 808
(2021/08/12)
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- Synthesis and potential antimicrobial activity of novel α-aminophosphonates derivatives bearing substituted quinoline or quinolone and thiazole moieties
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To develop novel antimicrobial agents, and based on the biologically active heterocyclic quinoline and thiazole substituted, a series of novel α-aminophosphonates (9a–h) and (10i–l) derivatives that incorporated quinoline or quinolone, and coumarylthiazole or 5-phenylthiazol-2-amine moieties were designed and synthesized via Kabachnik–Fields reaction in the presence of ionic liquid under ultrasound irradiation. All the new compounds were obtained in good yield with a simple workup and were confirmed using various spectroscopic methods. The in vitro antimicrobial activity of all synthesized compounds were screened in terms of MIC values against the selected strains of Gram-negative and Gram-positive bacteria and two fungal strains using the broth micro-dilution method. The results showed that most of the tested compounds showed moderate inhibitory activities against both Gram‐positive and ‐negative bacteria compared with reference drugs. The following compounds 9e, 9g, 9h, 9i and 9f, 9g, 9h, 10k, 10l are the most active against Gram-positive and Gram-negative bacteria strains, respectively, with MIC values ranging between 0.25 and 128 μg/mL. The synthesized compounds 9b, 9c, 9f, 9g, 9h, 10k, and 10l exhibited excellent antifungal inhibition with MIC values ranging between 0.25 and 32 μg/mL. Structure–activity relationship revealed that the presence of coumarylthiazole moiety and hydroxyl in the quinoline group increased the inhibitory activity against microbial strains pathogens. These results confirm that the synthesized compounds can be potential antimicrobial drugs candidate. [Figure not available: see fulltext.]
- Boukhari, Abbes,Djahoudi, Abdelghani,Litim, Bilal,Meliani, Saida
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- Lead Optimization of Influenza Virus RNA Polymerase Inhibitors Targeting PA-PB1 Interaction
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Influenza viruses are responsible for contagious respiratory illnesses in humans and cause seasonal epidemics and occasional pandemics worldwide. Previously, we identified a quinolinone derivative PA-49, which inhibited the influenza virus RNA-dependent RNA polymerase (RdRp) by targeting PA-PB1 interaction. This paper reports the structure optimization of PA-49, which resulted in the identification of 3-((dibenzylamino)methyl)quinolinone derivatives with more potent anti-influenza virus activity. During the optimization, the hit compound 89, which was more active than PA-49, was identified. Further optimization and scaffold hopping of 89 led to the most potent compounds 100 and a 1,8-naphthyridinone derivative 118, respectively. We conclusively determined that compounds 100 and 118 suppressed the replication of influenza virus and exhibited anti-influenza virus activity against both influenza virus types A and B in the range of 50% effective concentration (EC50) = 0.061-0.226 μM with low toxicity (50% cytotoxic concentration (CC50) >10 μM).
- Mizuta, Satoshi,Otaki, Hiroki,Ishikawa, Takeshi,Makau, Juliann Nzembi,Yamaguchi, Tomoko,Fujimoto, Takuya,Takakura, Nobuyuki,Sakauchi, Nobuki,Kitamura, Shuji,Nono, Hikaru,Nishi, Ryota,Tanaka, Yoshimasa,Takeda, Kohsuke,Nishida, Noriyuki,Watanabe, Ken
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supporting information
p. 369 - 385
(2021/12/27)
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- Discovery of new quinolines as potent colchicine binding site inhibitors: design, synthesis, docking studies, and anti-proliferative evaluation
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Discovering of new anticancer agents with potential activity against tubulin polymerisation is still a promising approach. Colchicine binding site inhibitors are the most relevant anti-tubulin polymerisation agents. Thus, new quinoline derivatives have been designed and synthesised to possess the same essential pharmacophoric features of colchicine binding site inhibitors. The synthesised compounds were tested in?vitro against a panel of three human cancer cell lines (HepG-2, HCT-116, and MCF-7) using colchicine as a positive control. Comparing to colchicine (IC50 = 7.40, 9.32, and 10.41 μM against HepG-2, HCT-116, and MCF-7, respectively), compounds 20, 21, 22, 23, 24, 25, 26, and 28 exhibited superior cytotoxic activities with IC50 values ranging from 1.78 to 9.19 μM. In order to sightsee the proposed mechanism of anti-proliferative activity, the most active members were further evaluated in?vitro for their inhibitory activities against tubulin polymerisation. Compounds 21 and 32 exhibited the highest tubulin polymerisation inhibitory effect with IC50 values of 9.11 and 10.5 nM, respectively. Such members showed activities higher than that of colchicine (IC50 = 10.6 nM) and CA-4 (IC50 = 13.2 nM). The impact of the most promising compound 25 on cell cycle distribution was assessed. The results revealed that compound 25 can arrest the cell cycle at G2/M phase. Annexin V and PI double staining assay was carried out to explore the apoptotic effect of the synthesised compounds. Compound 25 induced apoptotic effect on HepG-2 thirteen times more than the control cells. To examine the binding pattern of the target compounds against the tubulin heterodimers active site, molecular docking studies were carried out.
- Hagras, Mohamed,El Deeb, Moshira A.,Elzahabi, Heba S. A.,Elkaeed, Eslam B.,Mehany, Ahmed B. M.,Eissa, Ibrahim H.
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p. 640 - 658
(2021/02/26)
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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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- 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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- 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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- 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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p. 2140 - 2151
(2021/07/21)
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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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- Synthesis and characterization of biologically important quinoline incorporated triazole derivatives
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Triazoles are well recognized in literature for their significant biologically active heterocyclic compounds. Also the quinoline nucleus found in several natural products shows a varied biological activity. Keeping in the view of these observations, a novel series of 6/7/8-substtuted-2-[(5-((4-chlorophenoxy)methyl)-4H-1,2,4-triazol-3-yl)thio]quinoline-3-carbaldehydes and 6/7/8-substituted-2-[(5-(pyridin-4-yl)-4H-1,2,4-triazol-3-yl)thio]quinoline-carbaldehydes were synthesized by the condensation of 5-(4-chloro phenoxy methyl)-2,4-dihydro-1,2,4-triazole-3-thiones and 5-(pyridin-3-yl)-4H-1,2,4-triazole-3-thiols with 6/7/8-substituted-2-chloro quinoline-3-carbaldehydes. The new series were established by Mass, NMR and IR spectroscopy and were also screened for their antimicrobial activities. A few of the novel compounds exhibited tremendous bioactivities compared to that of normal drug.
- D'Souza, Vineetha Telma,Nayak, Janardhana,D'Mello, Desmond Edward,Dayananda
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- Potential antibacterial and antifungal activities of novel sulfamidophosphonate derivatives bearing the quinoline or quinolone moiety
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A series of new α-sulfamidophosphonate/sulfonamidophosphonate (4a–n) and cyclosulfamidophosphonate (5a–d) derivatives containing the quinoline or quinolone moiety was designed and synthesized via Kabachnik–Fields reaction in the presence of ionic liquid under ultrasound irradiation. This efficient methodology provides new 1,2,5-thiadiazolidine-1,1-dioxide derivatives 5a–d in one step and optimal conditions. The molecular structures of the novel compounds 4a–n and 5a–d were confirmed using various spectroscopic methods. All these compounds were evaluated for their in vitro antibacterial activity against Gram-negative (Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853) and Gram-positive (Staphylococcus aureus ATCC 27923) bacteria, in addition to three clinical strains (E. coli 1, P. aeruginosa 1, and S. aureus 1). Most of the tested compounds showed more potent inhibitory activities against both Gram-positive and -negative bacteria compared with the sulfamethoxazole reference. The following compounds, 4n, 4f, 4g, 4m, 4l, 4d, and 4e, are the most active sulfamidophosphonate derivatives. Furthermore, these molecules gave interesting zones of inhibition varying between 28 and 49 mm, against all tested bacterial strains, with a low minimum inhibitory concentration (MIC) value ranging from 0.125 to 8 μg/ml. All the synthesized derivatives were also evaluated for their in vitro antifungal activity against Fusarium oxyporum f. sp. lycopersici and Alternaria sp. The results revealed that all the synthesized compounds exhibited excellent antifungal inhibition and the compounds 4f, 4g, 4m, and 4i were the most potent derivatives with MIC values ranging from 0.25 to 1 μg/ml against the two tested fungal strains. The strongest inhibition of bacteria and fungi strains was detected by the effect of quinolone and sulfamide moieties.
- Bazine, Ismahene,Bendjedid, Samira,Boukhari, Abbes
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- Enantioselective synthesis of functionalized 1,4-dihydropyrazolo-[4′,3′:5,6]pyrano[2,3-: B] quinolines through ferrocenyl-phosphine-catalyzed annulation of modified MBH carbonates and pyrazolones
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An enantioselective synthesis of highly functionalized 1,4-dihydropyrazolo[4′,3′:5,6]pyrano[2,3-b]quinolines from modified MBH carbonates and pyrazolones via a chiral phosphine-mediated alkylation/annulation sequence has been realized. The chiral dihydropyrano[2,3-c]pyrazoles bearing bio-active condensed heterocycles were facilely formed in good chemical yields and with high to excellent enantioselectivity by utilizing low catalyst loading.
- Li, Jingyi,Ling, Fei,Lu, Yin-Jie,Shao, Bingxuan,Xiao, Xiao,Yang, Zehui,Zhong, Weihui
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supporting information
p. 4690 - 4693
(2021/05/19)
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- Transition-metal-free oxidative cyclization reaction of enynals to access pyrane-2-one derivatives
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A novel and efficient metal-free C-H functionalization of enynals is developed to synthesize α-pyrone derivatives via the formation of two C-O bonds. In this project, K2S2O8 has been introduced as an efficient oxygen source and C-H functionalization agent in regioselective oxidative cyclization reaction with a relatively broad substrate scope.
- Abbasi Kejani, Alireza,Ansari, Farzaneh,Armaghan, Mahsa,Balalaie, Saeed,Frank, Walter,Jafarpour, Farnaz,Khosravi, Hormoz
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supporting information
p. 4263 - 4267
(2021/05/31)
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- Design, synthesis, and molecular docking study of novel quinoline-based bis-chalcones as potential antitumor agents
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A novel series of quinoline-based symmetrical and unsymmetrical bis-chalcones was synthesized via a Claisen–Schmidt condensation reaction between 3-formyl-quinoline/quinolone derivatives with acetone or arylidene acetones, respectively, by using KOH/MeOH/H2O as a reaction medium. Twelve of the obtained compounds were evaluated for their in vitro cytotoxic activity against 60 different human cancer cell lines according to the National Cancer Institute protocol. Among the screened compounds, the symmetrical N-butyl bis-quinolinyl-chalcone 14g and the unsymmetrical quinolinyl-bis-chalcone 17o bearing a 7-chloro-substitution on the N-benzylquinoline moiety and 4-hydroxy-3-methoxy substituent on the phenyl ring, respectively, exhibited the highest overall cytotoxicity against the evaluated cell lines with a GI50 range of 0.16–5.45 μM, with HCT-116 (GI50 = 0.16) and HT29 (GI50 = 0.42 μM) (colon cancer) representing best-case scenarios. Notably, several GI50 values for these compounds were lower than those of the reference drugs doxorubicin and 5-FU. Docking studies performed on selected derivatives yielded very good binding energies in the active site of proteins that participate in key carcinogenic pathways.
- Insuasty, Daniel,García, Stephanie,Abonia, Rodrigo,Insuasty, Braulio,Quiroga, Jairo,Nogueras, Manuel,Cobo, Justo,Borosky, Gabriela L.,Laali, Kenneth K.
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- Synthesis and antimicrobial activities of thiadiazole containing quinoline derivatives
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A novel series of 1-[(substituted 2-chloroquinolin-3-yl)methylidene]-3-[substituted-5-phenyl-1,3,4-thiadiazol-2-yl] thioureas have been synthesized by acid catalyzed reaction between the 1-(5-substitued phenyl-1,3,4-thiadiazol-2-yl) thioureas and 6-substi
- Dayananda,Nayak, Janardhana,D'Souza, Vineetha Telma
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p. 633 - 638
(2021/09/28)
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- Synthesis, structure-activity relationship and molecular docking studies of novel quinoline-chalcone hybrids as potential anticancer agents and tubulin inhibitors
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A new series of quinoline-chalcone hybrids was synthesized. The structures of these compounds were characterized by spectroscopic methods including 1H and 13CNMR and mass spectroscopy. The cytotoxic activity of compounds was evaluated against four human cancer cell lines including A2780 (human ovarian carcinoma) and A2780/RCIS (Cisplatin resistant human ovarian carcinoma), MCF-7 (human breast cancer cells), MCF-7/MX (Mitoxantrone resistant human breast cancer cells) and normal Huvec cells. The structure-activity relationship of synthesized compounds is discussed. Among quinolines 5e, 5g and 5j possessing benzoyl group showed significant cytotoxic activity against both resistant cancer cells and their parents. Compounds 5g and 5j, demonstrated the most antiproliferative activity with IC50 values ranging from 2.32 to 22.4 μM. They were also identified as tubulin inhibitors and induced cell cycle arrest at G2/M phase and apoptosis. Compound 5j induced more arrest at G2/M phase in four cancer cell lines compared to compound 5g. Finally, molecular dynamics simulation and molecular docking studies of compound 5j into the colchicine-binding site of tubulin demonstrated the possible interaction of this compound in the active site of tubulin.
- Mirzaei, Salimeh,Hadizadeh, Farzin,Eisvand, Farhad,Mosaffa, Fatemeh,Ghodsi, Razieh
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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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- 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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- Discovery of triazoloquinoxaline as novel STING agonists via structure-based virtual screening
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Stimulator of interferon genes (STING) is an endoplasmic reticulum adaptor facilitating innate immune signaling. Activation of STING leads to expression of interferons (IFNs) and pro-inflammatory cytokines which is associated with antiviral and antitumor responses. It is imperative to discovery potent compounds that precisely modulate STING. Herein, we describe the discovery of triazoloquinoxaline 1a as a novel STING agonist via Structure-based Virtual Screening. Specifically, biochemical and cell-based assays suggested that 1a stimulated concentration-dependently mRNA expression of IFNβ, CXCL-10 and IL-6. Furthermore, 1a significantly induced phosphorylation of STING, TANK-binding kinases1 (TBK1) and interferon regulatory factor 3 (IRF3), suggesting the activation of STING and its downstream TBK1-IRF3 signaling axis. In addition, 1a activated secretion of secreted alkaline phosphatase (SEAP) in dose-dependent manner and EC50 was 16.77 ± 3.814 μM, which is comparable with EC50 of 2′3′-cGAMP (9.212 ± 2.229 μM). These studies revealed that 1a is a promising STING agonist possessing the potential to be further developed for antiviral and antitumor treatment.
- Chen, Kaixian,Hou, Hui,Liu, Xiaohong,Wu, Xiaolong,Yang, Ruirui,Zhang, Sulin,Zheng, Mingyue
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supporting information
(2020/05/29)
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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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- Synthesis and biological evaluation of some novel quinoline based chalcones as potent antimalarial, anti-inflammatory, antioxidant and antidiabetic agents
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The objective of the present study was to synthesize a series of some novel quinoline based methoxy substituted chalcones and to evaluate their in vitro antimalarial, anti-inflammatory, antioxidant and antidiabetic activitites. The quinoline based chalcon
- Peerzade, Nargisbano A.,Jadhav, Shravan Y.,Bhosale, Raghunath B.
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p. 959 - 964
(2020/03/24)
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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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- 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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- 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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- Catalytic formal [4 + 1] isocyanide-based cycloaddition: An efficient strategy for the synthesis of 1: H -cyclopenta [b] quinolin-1-one derivatives
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An unprecedented catalytic isocyanide-based cycloaddition of alkyl and aryl isocyanides with (Z)-2-(2-hydroxy-2-alkylvinyl)quinoline-3-carbaldehydes was developed for the direct and efficient synthesis of 1H-cyclopenta[b]quinolin-1-one derivatives. On the
- Motaghi, Milad,Khosravi, Hormoz,Balalaie, Saeed,Rominger, Frank
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supporting information
p. 275 - 282
(2019/01/10)
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- Discovery and optimization of thienopyridine derivatives as novel urea transporter inhibitors
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Urea transporters (UTs) play an important role in the urine concentrating mechanism and are recognized as novel targets for developing small molecule inhibitors with salt-sparing diuretic activity. Thienoquinoline derivatives, a class of novel UT-B inhibitors identified by our group, play a significant diuresis in animal model. However, the poor solubility and low bioavailability limited its further development. To overcome these shortcomings, the structure modification of thienoquinoline was carried out in this study, which led to the discovery of novel thienopyridine derivatives as specific urea transporter inhibitors. Further optimization obtained the promising preclinical candidate 8n with not only excellent inhibition effect on urea transporters and diuretic activity on rat model, but also suitable water solubility and Log P value.
- Zhao, Yan,Li, Min,Li, Bowen,Zhang, Shun,Su, Aoze,Xing, Yongning,Ge, Zemei,Li, Runtao,Yang, Baoxue
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p. 131 - 142
(2019/04/08)
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- Design of new quinolin-2-one-pyrimidine hybrids as sphingosine kinases inhibitors
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Sphingosine-1-phosphate is now emerging as an important player in cancer, inflammation, autoimmune, neurological and cardiovascular disorders. Abundance evidence in animal and humans cancer models has shown that SphK1 is linked to cancer. Thus, there is a
- Abonia, Rodrigo,Andújar, Sebastián,Cobo, Justo,Enriz, Ricardo D.,Gutiérrez, Lucas,Insuasty, Daniel,Lima, Santiago,Marchal, Antonio,Nogueras, Manuel,Spiegel, Sarah,Vettorazzi, Marcela
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- Design, synthesis and pharmacological evaluation of new 3-(1H-benzimidazol-2-yl)quinolin-2(1H)-one derivatives as potential antitumor agents
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A series of new 3-(1H-benzimidazol-2-yl)quinolin-2(1H)-one derivatives (5a1?5d6) were designed and synthesized as antitumor agents. In vitro antitumor assay results showed that some compounds exhibited moderate to high inhibitory activity against HepG2, SK-OV-3, NCI-H460 and BEL-7404 tumor cell lines, and most compounds exhibited much lower cytotoxicity against the HL-7702 normal cell line compared to 5-FU and cisplatin. In vivo antitumor assay results demonstrated that 5a3 exhibited effective inhibition on tumor growth in the NCI-H460 xenograft mouse model and that 5d3 displayed excellent antiproliferative activity in the BEL-7402 xenograft model. These results suggested that both 5a3 and 5d3 could be used as anticancer drug candidates. Mechanistic studies suggested that compounds 5a3 and 5d3 exerted their antitumor activity by up-regulation of Bax, intracellular Ca2+ release, ROS generation, downregulation of Bcl-2, activation of caspase-9 and caspase-3 and subsequent cleavage of PARP, inhibition of CDK activity and activation of the p53 protein.
- Kuang, Wen-Bin,Huang, Ri-Zhen,Qin, Jiao-Lan,Lu, Xing,Qin, Qi-Pin,Zou, Bi-Qun,Chen, Zhen-Feng,Liang, Hong,Zhang, Ye
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p. 139 - 150
(2018/08/09)
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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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- 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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- lH-Pyrazolo[3,4-b]quinolin-3-amine derivatives inhibit growth of colon cancer cells via apoptosis and sub G1 cell cycle arrest
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A series of lH-pyrazolo[3,4-b]quinolin-3-amine derivatives were synthesized and evaluated for anticancer efficacy in a panel of ten cancer cell lines, including breast (MDAMB-231 and MCF-7), colon (HCT-116, HCT-15, HT-29 and LOVO), prostate (DU-145 and PC3), brain (LN-229), ovarian (A2780), and human embryonic kidney (HEK293) cells, a non-cancerous cell line. Among the eight derivatives screened, compound QTZ05 had the most potent and selective antitumor efficacy in the four colon cancer cell lines, with IC50 values ranging from 2.3 to 10.2 μM. Furthermore, QTZ05 inhibited colony formation in HCT-116 cells in a concentration-dependent manner. Cell cycle analysis data indicated that QTZ05 caused an arrest in the sub G1 cell cycle in HCT-116 cells. QTZ05 induced apoptosis in HCT-116 cells in a concentration-dependent manner that was characterized by chromatin condensation and increase in the fluorescence of fluorochrome-conjugated Annexin V. The findings from our study suggest that QTZ05 may be a valuable prototype for the development of chemotherapeutics targeting apoptotic pathways in colorectal cancer cells.
- Karthikeyan, Chandrabose,Amawi, Haneen,Viana, Arabela Guedes,Sanglard, Leticia,Hussein, Noor,Saddler, Maria,Ashby, Charles R.,Moorthy, N.S. Hari Narayana,Trivedi, Piyush,Tiwari, Amit K.
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p. 2244 - 2249
(2018/05/31)
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- Synthesis, biological evaluation and computational study of new quinoline hybrids as antitubercular agent
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Background: Tuberculosis is global health threat caused by infectious bacillus called Mycobacterium tuberculosis. To develop newer antitubercular agents against bacterial resistance, we have designed new quinoline derivatives 6a-6f and 7a-7f by molecular hybridization approach and evaluated for antitubercular, antioxidant and cytotoxicity studies along with molecular docking study. Methods: The designed molecules were synthesized by multi-step synthetic protocol and structures of compounds were confirmed by NMR, Mass and Elemental analysis. The synthesized derivatives were screened for antitubercular activity against Mycobacterium tuberculosis using Microplate Alamar Blue Assay (MABA). The antioxidant activity and cytotoxicity were also evaluated using 1,1-Dipheny-1-picrylhydrazyl (DPPH) radical scavenging and Sulforhodamine B (SRB) assay, respectively. The molecular docking studies were performed in Glide v5.6 (Schrodinger). Results: Among the synthesized derivatives, the compounds 6d and 7d displayed promising antitubercular activity, with MIC value of 18.27 and 15.00 μM respectively and are relatively nontoxic to HeLa cell line. The synthesized compounds were found to have potential antioxidant activities with IC50 range of 73.47-123.46 μM. The molecular docking study, physicochemical and pharmacokinetic properties prediction study suggested that the synthesized derivatives have potential for development of good drug candidate. Conclusion: Herein, we designed and synthesized a series of new quinoline pharmacophores appended with isoniazid and linezolid-like fragment as a promising strategy for the development of quinoline derivatives with potent biological activities.
- Zaheer, Zahid,Shaikh, Sameer I.,Mokale, Santosh N.,Lokwani, Deepak K.
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p. 914 - 922
(2018/08/17)
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- Synthesis of Some 4-Quinolinyl Pyridines and their Antimicrobial and Docking Studies
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A series of some substituted diethyl 4-(2-chloroquinolin-3-yl)-2,6-dimethylpyridine-3,5-dicarboxylates has been synthesized from substituted diethyl4-(2-chloroquinolin-3-yl)-1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylates (1,4-DHPs) by treating the latter with SiO2–HNO3 which proved to be a better oxidant in terms of product yield, reaction time, and cost. Further, these compounds were screened for their antimicrobial activity. All the diethyl 4-(2-chloroquinolin-3-yl)-2,6-dimethylpyridine-3,5-dicarboxylates exhibited more potent activities than the corresponding 1,4-DHPs. Further, docking simulation of the most active and least active compounds 3e and 2e into Escherichia coli topoisomerase II DNA Gyrase B was also performed.
- Kumar, Ramesh,Khanna, Radhika,Kumar, Parvin,Kumar, Vikas,Kamboj, Ramesh C.
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p. 2740 - 2747
(2017/09/26)
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- Microwave-assisted synthesis of diversely substituted quinoline-based dihydropyridopyrimidine and dihydropyrazolopyridine hybrids
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An efficient, catalyst-free, and one-pot three-component procedure for the synthesis of novel and nitrogen rich dihydropyrido[2, 3-d]pyrimidines and dihydro-1H-pyrazolo[3, 4-b]pyridines bearing a quinoline pharmacophore fragment is provided. Reactions proceeded in DMF under microwave irradiation of three-component mixtures of formyl-quinoline derivatives, primary heterocyclic amines and cyclic 1, 3-diketones. Interestingly, when conventional heating at reflux was used for the starting 5-amino-1-phenylpyrazole, the corresponding aromatized pyrazolopyridines were obtained as the main products. Single crystal X-ray analysis confirmed unequivocally the structure of both the dihydro- and aromatized products.
- Insuasty, Daniel,Abonia, Rodrigo,Insuasty, Braulio,Quiroga, Jairo,Laali, Kenneth K.,Nogueras, Manuel,Cobo, Justo
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supporting information
p. 555 - 563
(2017/10/13)
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- Tetrazolylmethyl quinolines: Design, docking studies, synthesis, anticancer and antifungal analyses
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A new series of 2,5 and 1,5-regioisomers of the tetrazolyl group viz., 3-[(5-benzyl/benzylthio-2H-tetrazol-2-yl) methyl]-2-chloro-6-substituted quinoline 6h-q and 3-[(5-benzyl/benzylthio-1H-tetrazol-1-yl) methyl]-2-chloro-6-substituted quinolines 7h-q were synthesized. Docking studies of all these compounds with DNA as target using PDB: 1AU5 and 453D revealed that the compounds 6h and 6i act as covalent cross linker on the DNA helix of the former and intercalate the latter both with higher C score values. Another set of docking studies in the active pocket of dihydrofolate reductase and N-myristoyl transferase as targets to assess antifungal activity revealed that compounds 6k, 6l, 6p and 7q (with bromo and fluro substituents) showcases different binding modes and hydrogen bonding. Further, the compounds were screened for anticancer activity (primary cytotoxicity) against NCI-60 Human tumor cell line at a single high dose (10?5M) concentration assay. Among the tested compounds, 6h has shown 99.28% of GI against Melanoma (SK-MEL-5) and compound 6i has shown 97.56% of GI against Breast Cancer (T-47D). Further, in vitro antifungal assay against A. fumigatus and C. albicans for these compounds 6h-q and 7h-q revealed potential to moderate activities as compared to the standard.
- Shaikh, Saba Kauser J.,Kamble, Ravindra R.,Somagond, Shilpa M.,Devarajegowda,Dixit, Sheshagiri R.,Joshi, Shrinivas D.
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supporting information
p. 258 - 273
(2017/02/15)
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- A Schmidt rearrangement-mediated synthesis of novel tetrahydro-benzo[1,4]diazepin-5-ones as potential anticancer and antiprotozoal agents
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Novel tetrahydro-5H-benzo[e][1,4]diazepin-5-ones, several of them, containing the quinoline pharmacophore, were synthesized via a Schmidt rearrangement from their corresponding 1,2,3,4-tetrahydro-4-quinolones mediated by the NaN3/H2SO4 reaction conditions. Twelve of the obtained compounds were in vitro screened by the US National Cancer Institute (NCI) for their ability to inhibit 60 different human tumor cell lines, where compound 24a presented a remarkable activity against 58 of the 60 cancer cell lines, with the most important GI50 values ranging from 0.047 to 8.16 μM and LC50 values ranging from 9.4 to > 100 μM. Additionally, some of them were evaluated as antimalarial, antitrypanosomal and antileishmanial agents. The best antimalarial response was observed for compound 22g with an EC50 = 13.61 μg/mL for Plasmodium falciparum, while compound 24d exhibited high activity against Trypanosoma cruzi. and Leishmania (V) panamensis with EC50 = 2.78 μg/mL and 3.35 μg/mL respectively.
- Insuasty, Daniel,Robledo, Sara M.,Vélez, Iván D.,Cuervo, Paola,Insuasty, Braulio,Quiroga, Jairo,Nogueras, Manuel,Cobo, Justo,Abonia, Rodrigo
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p. 567 - 583
(2017/11/03)
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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; 00140
(2017/07/14)
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- Design, synthesis and evaluation of 3-quinoline carboxylic acids as new inhibitors of protein kinase CK2
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In this article, the derivatives of 3-quinoline carboxylic acid were studied as inhibitors of protein kinase CK2. Forty-three new compounds were synthesized. Among them 22 compounds inhibiting CK2 with IC50 in the range from 0.65 to 18.2 μM were identified. The most active inhibitors were found among tetrazolo-quinoline-4-carboxylic acid and 2-aminoquinoline-3-carboxylic acid derivatives.
- Syniugin, Anatolii R.,Ostrynska, Olga V.,Chekanov, Maksym O.,Volynets, Galyna P.,Starosyla, Sergiy A.,Bdzhola, Volodymyr G.,Yarmoluk, Sergiy M.
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p. 160 - 169
(2016/12/22)
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- Novel tetrazoloquinoline-rhodanine conjugates: Highly efficient synthesis and biological evaluation
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In search of new active molecules against Mycobacterium tuberculosis (MTB) H37Ra and Mycobacterium bovis BCG, a small focused library of rhodanine incorporated tetrazoloquinoline has been efficiently synthesized by using [HDBU][HSO4] acidic ionic liquid. The compound 3c found to be promising inhibitor of MTB H37Ra and M. bovis BCG characterized by lower MIC values 4.5 and 2.0 μg/mL, respectively. The active compounds were further tested for cytotoxicity against HeLa, THP-1, A549 and PANC-1 cell lines using MTT assay and showed no significant cytotoxic activity at the maximum concentration evaluated. Again, the synthesized compounds were found to have potential antifungal activity. Furthermore, to rationalize the observed biological activity data, the molecular docking study also been carried out against a potential target Zmp1 enzyme of MTB H37Ra, which revealed a significant correlation between the binding score and biological activity for these compounds. The results of in vitro and in silico study suggest that these compounds possess ideal structural requirement for the further development of novel therapeutic agents.
- Subhedar, Dnyaneshwar D.,Shaikh, Mubarak H.,Nawale, Laxman,Yeware, Amar,Sarkar, Dhiman,Khan, Firoz A. Kalam,Sangshetti, Jaiprakash N.,Shingate, Bapurao B.
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p. 2278 - 2283
(2016/04/20)
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- Novel tetrazoloquinoline-thiazolidinone conjugates as possible antitubercular agents: Synthesis and molecular docking
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A novel approach for the synthesis of a new 4-thiazolidinone scaffold was developed by a one-pot three-component cyclocondensation of various tetrazolo quinoline aldehydes 1a-f, acid hydrazide 2a-c, and thioglycolic acid 3 in the presence of [DBUH][OAc] as a catalyst in high yields. All the conjugates were screened for their antimycobacterial activity against MTB H37Ra and M. bovis BCG strains, with the MIC values ranging from 0.99-13.55 μmol mL-1 and 0.14-20.11 μmol mL-1, respectively. The 4-thiazolidinone-incorporated tetrazoloquinoline derivatives 4a, 4d, 4g, 4j, 4m, and 4p were highly potent against MTB H37Ra and M. bovis BCG strains. The most active compounds were also evaluated for their cytotoxicity against MCF-7, A549, and HCT 116 cell lines and were found to be non-cytotoxic. Further, molecular docking studies into the active site of the InhA enzyme revealed a similar binding mode to the native ligand in the crystal structure, thereby helping us to understand the ligand-protein binding interaction and establish a structural basis for the inhibition of mycobacterium tuberculosis. The results suggest that the tetrazoloquinoline-thiazolidinone conjugates 4a, 4d, 4g, 4j, 4m, and 4p are promising antitubercular agents.
- Subhedar, Dnyaneshwar D.,Shaikh, Mubarak H.,Shingate, Bapurao B.,Nawale, Laxman,Sarkar, Dhiman,Khedkar, Vijay M.
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p. 1832 - 1848
(2016/09/28)
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- Novel amalgamation of phthalazine–quinolines as biofilm inhibitors: One-pot synthesis, biological evaluation and in silico ADME prediction with favorable metabolic fate
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A facile and highly efficient one-pot synthesis of phthalazine–quinoline derivatives is reported via four component reaction of phthalic anhydride, hydrazine hydrate, 5,5-dimethyl 1,3 cyclohexanedione and various quinoline aldehydes using PrxCoFe2?xO4(x?=?0.1) nanoparticles as a catalyst. The synthesized compounds have been evaluated for anti-biofilm activity against Pseudomonas aeruginosa and Candida albicans. The compounds 12a (IC50?=?30.0?μM) and 12f (IC50?=?34.5?μM) had shown promising anti-biofilm activity against P. aeruginosa and C. albicans, respectively, when compared with standards without affecting the growth of cells (and thus behave as anti-quorum sensing agents). Compounds 12a (MIC?=?45.0?μg/mL) and 12f (MIC?=?57.5?μg/mL) showed significant potent antimicrobial activity against P. aeruginosa and C. albicans, respectively. Thus, the active derivatives were not only potent biofilm inhibitors but also efficient antimicrobial agents. In silico ADME and metabolic site prediction studies were also held out to set an effective lead candidate for the future antimicrobial drug discovery initiatives.
- Zaheer, Zahid,Khan, Firoz A. Kalam,Sangshetti, Jaiprakash N.,Patil, Rajendra H.,Lohar
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p. 1696 - 1703
(2016/07/27)
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- Synthesis and antimicrobial activity of azetidin-2-one fused 2-chloro-3-formyl quinoline derivatives
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Azetidin-2-one fused 2-chloro-3-formyl quinolines derivatives, 3-chloro-4-(2-chloro-8/7/6-methoxyquinolin-3-yl)-1-(2,4-dinitro/4-nitro phenylamino)azetidin-2-one,3-chloro-4-(2-chloro-8/7/6-chloroquinolin-3-yl)-1-(2,4-dinitro/4-nitro phenylamino)azetidin-2-one, 3-chloro-4-(2-chloro-8/7/6-methylquinolin-3-yl)-1-(2,4-dinitro/4-nitrophenylamino) azetidin-2-one were synthesized by four steps, respectively from N-arylacetamides, 2-chloro-3-formyl quinolines, 2,4-dinitro/4-nitro phenyl hydrazine reflux with chloroacetyl chloride and triethyl amine. However yields of quinolines having electron donating groups in all cases. The structures of the synthesized compounds have been established on the basis of physical and spectral data. The antibacterial and antifungal activity of these compounds was tested by filter paper disc method against Staphylococcus aureus (MTCC96), Escherichia coli (MTCC722) and Candida albicans (MTCC183). The results showed that azetidin-2-one fused 2-chloro-3-formyl quinolines derivatives are better in inhibiting the growth of both types of organisms. Compounds AZT b2, AZT b3 to AZT g2, AZT g3 were found to be more potent compared to standard drug.
- Nayak, Govind,Shrivastava, Birendra,Singhai, Akhlesh Kumar
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p. 1977 - 1982
(2016/10/24)
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- Modified procedure for the synthesis of 2-chloroquinoline-3-carbaldehydes using phosphorus pentachloride
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An alternative, convenient, and efficient procedure for the synthesis of 2-chloroquinoline-3-carbaldehyde was carried out by the action of Vilsmeiers reagent on acetanilides using phosphorus pentachloride as chlorinating agent in place of phosphoryl chloride, obtaining good yields for activated acetanilides. The optimal conditions for this reaction requires only 4.5 equivalents of phosphorus pentachloride, 3 equivalents of N,N-dimethylformamide, and 1 equivalent of the corresponding acetanilide at 100 °C for approximately 4 h.
- Romero, Angel H.
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supporting information
p. 287 - 291
(2016/03/09)
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- Molecular and Nanoaggregation in Cyclometalated Iridium(III) Complexes through Structural Modification
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New terpyridyl ligands TP1, TP2 and cyclometalated iridium(III) complexes 1 and 2 based on these ligands have been synthesized. The ligands and complexes have been characterized by elemental analysis and spectroscopic studies (ESI-MS,1H and13C NMR, UV/Vis, fluorescence). The molecular structure of 1 has been verified by X-ray single-crystal analysis. It has been unambiguously established that variation of the substituents on 1 and 2 leads to molecular aggregation in 1, while 2 remains nonaggregated. Furthermore, complexes 1 and 2 have been successfully utilized as capping agents for the stabilization of gold nanoparticles (AuNPs). It is of note that 1 forms discretely, while 2 aggregates AuNPs through the assemblage of ultrasmall nanoparticles. It has been affirmed by1H NMR titration studies that –NH groups from 1 and 2 are involved in the capping of AuNPs. The role of simple structural variations in directing molecular and nanoaggregation has been clearly established for the first time by spectroscopic (UV/Vis, fluorescence,1H NMR titration) and morphological studies [SEM, TEM, EDX (energy-dispersive X-ray), DLS (dynamic light scattering)].
- Mukhopadhyay, Sujay,Singh, Roop Shikha,Biswas, Arnab,Maiti, Biswajit,Pandey, Daya Shankar
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p. 4199 - 4206
(2016/09/16)
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- Synthesis and bio-evaluation of novel quinolino-stilbene derivatives as potential anticancer agents
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A series of 25 novel quinolino-stilbene derivatives were designed, synthesized and evaluated for their potential as anticancer agents. Three of them not only displayed quite potent antiproliferative activity with IC50 values 50 values in the range of 4-10 μM, and the rest was moderately active or inactive. One of these viz. 3-[E-(4-fluorostyryl)]-2-chloroquinoline (compound 7B) caused substantial DNA damage and arrested cell cycle in S phase. Interestingly, 7B was very active against MDA-MB468 (IC50 = 0.12 μM), but not against other cell lines examined. Compound 3-[Z-(3-(trifluoromethyl)styryl)]-2-chloroquinoline (12A), the most effective against all cancer cell lines examined, caused prolonged cell cycle arrest at mitosis and eventually apoptosis. Data from an in vitro study showed that compound 12A inhibited microtubule polymerization in a similar fashion to nocodazole. Further study using in silico molecular modeling revealed that 12A causes the impediment of microtubule polymerization by binding to tubulin at the same cavity where podophyllotoxin binds.
- Srivastava, Vandana,Lee, Hoyun
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p. 7629 - 7640
(2015/12/18)
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