- Synthesis and Anti-Arrhythmic Activity of the Chloride and Salicylate Salts of Morpholinoacetic Acid Ortho-Toluidide
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Acylation of ortho-toluidine hydrochloride by chloroacetylchloride followed by amination by morpholine in the presence of an excess of Et3N produced morpholinoacetic acid ortho-toluidide and its salicylate salt. The acute toxicity and anti-arrh
- Gashkova,Rudakova,Syropyatov, B. Ya.
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- Synthesis and Biological Evaluation of Dithiobisacetamides as Novel Urease Inhibitors
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Thirty-eight disulfides containing N-arylacetamide were designed and synthesized in an effort to develop novel urease inhibitors. Biological evaluation revealed that some of the synthetic compounds exhibited strong inhibitory potency against both cell-free urease and urease in intact cell with low cytotoxicity to mammalian cells even at concentration up to 250 μM. Of note, 2,2′-dithiobis(N-(2-fluorophenyl)acetamide) (d7), 2,2′-dithiobis(N-(3,5-difluorophenyl)acetamide) (d24), and 2,2′-dithiobis(N-(3-fluorophenyl)acetamide) (d8) were here identified as the most active inhibitors with IC50 of 0.074, 0.44, and 0.81 μM, showing 32- to 355-fold higher potency than the positive control acetohydroxamic acid. These disulfides were confirmed to bind urease without covalent modification of the cysteine residue and to inhibit urease reversibly with a mixed inhibition mechanism. They also showed very good anti-Helicobacter pylori activities with d8 showing a comparable potency to the clinical used drug amoxicillin. The impressive in vitro biological profile indicated their immense potential as therapeutic agents to tackle H. pylori caused infections.
- Liu, Mei-Ling,Li, Wei-Yi,Fang, Hai-Lian,Ye, Ya-Xi,Li, Su-Ya,Song, Wan-Qing,Xiao, Zhu-Ping,Ouyang, Hui,Zhu, Hai-Liang
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- N-Aryl mercaptoacetamides as potential multi-target inhibitors of metallo-β-lactamases (MBLs) and the virulence factor LasB fromPseudomonas aeruginosa
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Increasing antimicrobial resistance is evolving to be one of the major threats to public health. To reduce the selection pressure and thus to avoid a fast development of resistance, novel approaches aim to target bacterial virulence instead of growth. Another strategy is to restore the activity of antibiotics already in clinical use. This can be achieved by the inhibition of resistance factors such as metallo-β-lactamases (MBLs). Since MBLs can cleave almost all β-lactam antibiotics, including the “last resort” carbapenems, their inhibition is of utmost importance. Here, we report on the synthesis andin vitroevaluation ofN-aryl mercaptoacetamides as inhibitors of both clinically relevant MBLs and the virulence factor LasB fromPseudomonas aeruginosa. All testedN-aryl mercaptoacetamides showed low micromolar to submicromolar activities on the tested enzymes IMP-7, NDM-1 and VIM-1. The two most promising compounds were further examined in NDM-1 expressingKlebsiella pneumoniaeisolates, where they restored the full activity of imipenem. Together with their LasB-inhibitory activity in the micromolar range, this class of compounds can now serve as a starting point for a multi-target inhibitor approach against both bacterial resistance and virulence, which is unprecedented in antibacterial drug discovery.
- Brunst, Steffen,Ducho, Christian,Frank, Denia,Hirsch, Anna K. H.,Kramer, Jan S.,Proschak, Ewgenij,Rotter, Marco,Voos, Katrin,Weizel, Lilia,Wichelhaus, Thomas A.,Yahiaoui, Samir,Haupenthal, J?rg
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supporting information
p. 1698 - 1708
(2021/11/23)
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- Synthesis of novel 1,2,3-triazoles bearing 2,4 thiazolidinediones conjugates and their biological evaluation
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Searching for new active molecules against M. Bovis BCG and Mycobacterium tuberculosis (MTB) H37Ra, a focused of 1,2,3-triazoles-incorporated 2,4 thiazolidinedione conjugates have been efficiently prepared via a click chemistry approach cyclocondensation of 4-amino-N-(5-methylisoxazol-3-yl)benzenesulfonamide (4), aryl aldehyde (5a–l), and mercapto acetic acid (6) with good to promising yields. The newly synthesized compounds were tested against drug-sensitive MTB and BCG. In particular, compounds 8g, 8h, 8j and 8l are highly potent against both the strains with IC90 values in the range of 1.20–2.70 and 1.24–2.65?μg/mL, respectively. Based on the results from the antitubercular activity, SAR for the synthesized series has been developed. Most of the active compounds were non-cytotoxic against MCF-7, HCT 116 and A549 cell lines. Most active compounds were having a higher selectively index, which suggested that these compounds were highly potent.
- Kulkarni, Pravin S.,Karale, Sanjay N.,Khandebharad, Amol U.,Agrawal, Brijmohan R.,Sarda, Swapnil R.
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p. 2035 - 2046
(2021/02/05)
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- Synthesis of (2-chloroquinolin-3-yl)-1,3,4-thiadiazole-2-carboxamides
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(2-Chloroquinolin-3-yl)-1,3,4-thiadiazole-2-carboxamides were synthesized from hydrazones obtained via the reaction of 3-formyl-2-chloroquinoline with oxamic acid thiohydrazides.
- Aksenov, A. N.,Krayushkin, M. M.,Yarovenko, V. N.
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p. 1131 - 1134
(2021/07/21)
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- Synthesis, Characterization and Thermal Study of some new Organochalcogenide compounds containing arylamide group
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Two Series of organochalcogen compounds were prepared. The first series was prepared by the reaction of 2-chloro-N-arylacetamide (where aryl is benzyl, phenyl, o-toluene, or p-toluene) with sodium hydrogen selenide (prepared in situ) to give diorganyl selenide compounds (R2Se). The second series was prepared by reaction of N-benzyl-2-chloro-N-(2-chloroacetyl) acetamide with sodium chalcogenate, Na2E (where E= S, Se, and Te) to give the corresponding cyclic chalcogenide compounds. Diiodo derivatives of cyclic selenide and telluride were also prepared. The thermal stability of the new selenium compounds (R2Se) were decomposed at 300°C. Thermogram showed a phase transfer point between 120-150°C indicating that these compounds may act as liquid crystal compounds. All new compounds were characterized by CHN elemental analysis, UV-Visible, FT-IR and 1H NMR spectroscopic data.
- Hassan,Abdulwahid,Al-Luaibi,Al-Jadaan
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p. 5009 - 5015
(2021/08/31)
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- A copper-catalyzed synthesis of aryloxy-tethered symmetrical 1,2,3-triazoles as potential antifungal agents targeting 14 α-demethylase
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The search for potent therapeutic agents has prompted the design and synthesis of a library of twenty-six aryloxy-tethered and amide-linked symmetrical 1,2,3-triazoles (8a-z) using a copper(i)-catalyzed click chemistry approach. All the synthesized compounds have been screened for theirin vitroantifungal activity against four different fungal strains as well as the enzymatic study for the inhibition of 14 α-demethylase enzyme. The bioactivity results show that most of the synthesized compounds were found to be better antifungal agents as compared to Miconazole. Among them, compound8ashowed the most promising antifungal activity against all the tested fungal strains. Furthermore, the enzymatic study reveals that compounds8iand8oare the most promising inhibitors of the 14 α-demethylase enzyme. In support of these results, the molecular docking study of the synthesized molecules against the sterol 14 α-demethylase (CYP51) could provide the structural basis for the antifungal activity. These compounds have also been analyzed for the ADME properties.
- Deshmukh, Tejshri R.,Jadhav, Rohit G.,Khedkar, Vijay M.,Sangshetti, Jaiprakash N.,Sarkate, Aniket P.,Shingate, Bapurao B.,Tiwari, Shailee V.
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supporting information
p. 13104 - 13118
(2021/08/03)
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- New Mercaptoacetamide Derivatives: Synthesis and Assessment as Antimicrobial and Antimycobacterial Agents
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During last few years, the frightening elevation of bacterial resistance was accompanied by dramatic decline in recent treatments of infectious diseases, which became a point of anxiety for healthcare industries. MDR and XDR strains of Mycobacterium tuberculosis (Mtb) result in the tuberculosis. In this regard, herein, a series of new mercaptoacetamide derivatives were synthesized via multipot synthetic pathway and the rationale was the appraisal of bioactivity in compact heteronuclei and their assessment as potential antimicrobial and antimycobacterial agents against virulent strain of Mtb, H37Ra for structure–activity relationship (SAR) studies. The inhibition zones of compounds 4c and 4e were found to be nearest to that of standard drug Ciprofloxacin, while compounds 4h and 4j were mild to moderately active against Gram positive bacteria (Staphylococcus aureus, Streptococus pneumonia) and Gram negative bacteria (Pseudomonas aeruginosa, Salmonella typhimurium and Escherichia coli). MIC90 assays indicated that new mercaptoacetamides did not exhibit in vitro activity against Mtb in contrast to Rifampicin and Streptomycin, first-line antimycobacterial chemotherapeutic agents. According to the present study, it was concluded that mercaptoacetamides of the new series succeeded as antimicrobial agents but could not develop as potential lead compounds against Mtb when tested in concentrations of 50, 25, 12.5 and 6.25 μg/mL.
- Hashim, Syed Riaz,Hegde, Rahul Rama,Pal, Dilipkumar,Rani, Priyanka
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p. 715 - 723
(2021/10/27)
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- Synthesis and biological evaluation of 1,2,3-triazole tethered thymol-1,3,4-oxadiazole derivatives as anticancer and antimicrobial agents
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A library of 1,2,3-triazole-incorporated thymol-1,3,4-oxadiazole derivatives (6–18) hasbeen synthesized and tested for anticancer and antimicrobial activities. Compounds 7, 8, 9, 10, and 11 exhibited significant antiproliferative activity. Among these act
- Ahmad, Abrar,Alam, Mohammad Mahboob,Alfaifi, Sulaiman Y. M.,Alghamdi, Abdullah A. A.,Ali, Nada M.,Almalki, Abdulraheem S. A.,Alsharif, Meshari A.,Elhenawy, Ahmed A.,Malebari, Azizah M.,Nazreen, Syed
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- Synthesis of Some New Acetanilide Derivatives as COX Inhibitors and Assessment of Analgesic/Anti-Inflammatory Activities
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The purpose of the present research was to synthesize a new series of acetanilide derivatives that would have analgesic and anti-inflammatory properties in laboratory animals (rats). IR spectroscopy, 1HNMR spectroscopy and Mass spectroscopy wer
- Kumar, Arvind,Mishra, Arun K.,Singh, Rajib Kumar
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p. 1475 - 1487
(2022/01/24)
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- Naproxen based 1,3,4-oxadiazole derivatives as EGFR inhibitors: Design, synthesis, anticancer, and computational studies
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A library of novel naproxen based 1,3,4-oxadiazole derivatives (8–16 and 19–26) has been synthesized and screened for cytotoxicity as EGFR inhibitors. Among the synthesized hy-brids, compound2-(4-((5-((S)-1-(2-methoxynaphthalen-6-yl)ethyl)-1,3,4-oxadiazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)phenol(15) was the most potent compound against MCF-7 and HepG2cancer cells with IC50 of 2.13 and 1.63 μg/mL, respectively, and was equipotent to doxorubicin (IC50 1.62 μg/mL) towards HepG2. Furthermore, compound 15 inhibited EGFR kinase with IC50 0.41 μM compared to standard drug Erlotinib (IC50 0.30 μM). The active compound induces a high percentage of necrosis towards MCF-7, HePG2 and HCT 116 cells. The docking studies, DFT and MEP also supported the biological data. These results demonstrated that these synthesized naproxen hybrids have EGFR inhibition effects and can be used as leads for cancer therapy.
- Alam, Mohammad Mahboob,Alfaifi, Mohammad Y.,Alfaifi, Sulaiman Y. M.,Almalki, Abdulraheem S. A.,Alsenani, Nawaf I.,Alsharif, Meshari A.,Elbehairi, Serag Eldin I.,Elhenawy, Ahmed A.,Malebari, Azizah M.,Nazreen, Syed
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- Antidiabetic compounds
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Compounds for the treatment of hyperglycemia and/or diabetes are provided. The compounds, which inhibit the enzyme dipeptidyl peptidase (DPP-4), are based on the structure where X may be present or absent an may be OH, Ar is an aryl group; and n ranges from 0 to 5.
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Page/Page column 13-14
(2020/06/16)
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- Design, synthesis and biological evaluation of novel naturally-inspired multifunctional molecules for the management of Alzheimer's disease
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In our overall goal to overcome the limitations associated with natural products for the management of Alzheimer's disease and to develop in-vivo active multifunctional cholinergic inhibitors, we embarked on the development of ferulic acid analogs. A systematic SAR study to improve upon the cholinesterase inhibition of ferulic acid with analogs that also had lower logP was carried out. Enzyme inhibition and kinetic studies identified compound 7a as a lead molecule with preferential acetylcholinesterase inhibition (AChE IC50 = 5.74 ± 0.13 μM; BChE IC50 = 14.05 ± 0.10 μM) compared to the parent molecule ferulic acid (% inhibition of AChE and BChE at 20 μM, 15.19 ± 0.59 and 19.73 ± 0.91, respectively). Molecular docking and dynamics studies revealed that 7a fits well into the active sites of AChE and BChE, forming stable and strong interactions with key residues Asp74, Trp286, and Tyr337 in AChE and with Tyr128, Trp231, Leu286, Ala328, Phe329, and Tyr341 in BChE. Compound 7a was found to be an efficacious antioxidant in a DPPH assay (IC50 = 57.35 ± 0.27 μM), and it also was able to chelate iron. Data from atomic force microscopy images demonstrated that 7a was able to modulate aggregation of amyloid β1-42. Upon oral administration, 7a exhibited promising in-vivo activity in the scopolamine-induced AD animal model and was able to improve spatial memory in cognitive deficit mice in the Y-maze model. Analog 7a could effectively reverse the increased levels of AChE and BChE in scopolamine-treated animals and exhibited potent ex-vivo antioxidant properties. These findings suggest that 7a can act as a lead molecule for the development of naturally-inspired multifunctional molecules for the management of Alzheimer's and other neurodegenerative disorders.
- Chittiboyina, Amar G.,Doerksen, Robert J.,Modi, Gyan,Nayak, Prasanta Kumar,Pandey, Amruta,Pandey, Pankaj,Priya, Khushbu,Rai, Geeta,Shankar, Gauri,Singh, Yash Pal,Tej, Gullanki Naga Venkata Charan,Vishwakarma, Swati
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- New N-phenylacetamide-linked 1,2,3-triazole-tethered coumarin conjugates: Synthesis, bioevaluation, and molecular docking study
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A series of new 1,2,3-triazole-tethered coumarin conjugates linked by N-phenylacetamide was efficiently synthesized via the click chemistry approach in excellent yields. The synthesized conjugates were evaluated for their in vitro antifungal and antioxida
- Akolkar, Satish V.,Nagargoje, Amol A.,Shaikh, Mubarak H.,Warshagha, Murad Z. A.,Sangshetti, Jaiprakash N.,Damale, Manoj G.,Shingate, Bapurao B.
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- Dual targeting of cholinesterase and amyloid beta with pyridinium/isoquinolium derivatives
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With the surge in the cases of Alzheimer's disease (AD) over the years, several targets have been explored to curb the disease. Cholinesterases, namely acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), remain to be the available targets that are amendable to currently approved treatments. In this study, a series of novel compounds based on tramiprosate, a highly specific amyloid beta (Aβ) inhibitor, was designed to inhibit AChE, BuChE, and Aβ aggregation. In particular, the addition of a pyridinium/isoquinolinium ring to the tramiprosate moiety (to give compounds 3a–j) led to an increase in the binding affinity for the catalytic active site of cholinesterase, which was hampered by the presence of sulfonic acid. Exclusion of the sulfonic acid moiety led to a novel but effective class of cholinesterase inhibitors (9a–w). in vitro Aβ aggregation inhibition assay indicated that compounds 3a–j, 9e–f, 9i–l, 9q, 9r, 9u–w, and 12 could inhibit over 10% Aβ aggregation at 1 mM concentration. Cholinesterase inhibition assay suggested that compounds 9g, 9h, 9o, and 9q–t exhibit over 70% inhibition on both AChE and BuChE at a concentration of 100 μM. Amongst the designed molecules, compound 9r (ca 18% at 1 mM) showed comparable inhibitory effect on the inhibition of Aβ aggregation with tramiprosate (ca 20% at 1 mM), along with impressive cholinesterase inhibitory potential (AChE IC50 = 13 μM and BuChE IC50 = 12 μM), acceptable toxicity and ability to pass through blood brain barrier, which could be used to ameliorate the phenotypes of AD in preclinical models.
- Chakravarty, Harapriya,Ju, Yaojun,Chen, Wen-Hua,Tam, Kin Y.
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p. 242 - 255
(2019/12/27)
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- Design and synthesis of 2,4-dioxochroman-pyridinium-phenylacetamide derivatives as new anti-Alzheimer agents: in vitro and in silico studies
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2,4-Dioxochroman-pyridinium-phenylacetamide derivatives 7a–n were synthesized and evaluated for their in vitro cholinesterase (ChE) inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Obtained results demonstrated that, among the synthesized compounds, two compounds, 7j and 7k, were more potent than the standard drug donepezil against BuChE and did not show cytotoxicity and carcinogenicity. Furthermore, through molecular modeling and molecular dynamic studies. we showed that these compounds can be located deep in the gorge cavity of BuChE and that they interacted with catalytic residues, acyl, and cholin-binding pockets of this enzyme. Support information.
- Mollazadeh, Marjan,Mohammadi-Khanaposhtani, Maryam,Azizian, Homa,Zonouzi, Afsaneh,Abdolahi, Zahra,Nadri, Hamid,Larijani, Bagher,Biglar, Mahmood,Mahdavi, Mohammad
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p. 1910 - 1928
(2020/06/17)
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- Development of triazolothiadiazine derivatives as highly potent tubulin polymerization inhibitors: Structure-activity relationship, in vitro and in vivo study
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Based on our prior work, we reported the design, synthesis, and biological evaluation of fifty-two new triazolothiadiazine-based analogues of CA-4 and their preliminary structure-activity relationship. Among synthesized compounds, Iab was found to be the most potent derivative possessing IC50 values ranging from single-to double-digit nanomolar in vitro, and also exhibited excellent selectivity over the normal human embryonic kidney HEK-293 cells (IC50 > 100 μM). Further mechanistic studies revealed that Iab significantly blocked tubulin polymerization and disrupted the intracellular microtubule network of A549 cells. Moreover, Iab induced G2/M cell cycle arrest by regulation of p-cdc2 and cyclin B1 expressions, and caused cell apoptosis through up-regulating cleaved PARP and cleaved caspase-3 expressions, and down-regulating of Bcl-2. Importantly, in vivo, Iab effectively suppressed tumor growth of A549 lung cancers in a xenograft mouse model without obvious signs of toxicity, confirming its potential as a promising candidate for cancer treatment.
- Ma, Weifeng,Chen, Peng,Huo, Xiansen,Ma, Yufeng,Li, Yanhong,Diao, Pengcheng,Yang, Fang,Zheng, Shengquan,Hu, Mengjin,You, Wenwei,Zhao, Peiliang
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- Synthesis and Quantification of 2-(Diethylamino)-N-(2-methylphenyl)acetamide Nitrate
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A procedure for the synthesis of 2-(diethylamino)-N-(2-methylphenyl)acetamide nitrate (monomecaine) exhibiting a pronounced antiarrhythmic activity has been optimized. A procedure for its identification and quality control of the drug substance by HPLC ha
- Chekryshkina,Demin,Tumashov,Babikova,Slepova
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p. 1532 - 1538
(2019/12/28)
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- Cink4T, a quinazolinone-based dual inhibitor of Cdk4 and tubulin polymerization, identified via ligand-based virtual screening, for efficient anticancer therapy
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Inhibition of cyclin dependent kinase 4 (Cdk4) prevents cancer cells from entering the early G0/G1 phase of the cell division cycle whereas inhibiting tubulin polymerization blocks cancer cells’ ability to undergo mitosis (M) late in the cell cycle. We had reported earlier that two non-planar and relatively non-toxic fascaplysin derivatives, an indole and a tryptoline, inhibit Cdk4 with IC50 values of 6.2 and 10 μM, respectively. Serendipitously, we had also found that they inhibited tubulin polymerization. The molecules were efficacious in mouse tumor models. We have now identified Cink4T in a 59-compound quinazolinone library, designed on the basis of ligand-based virtual screening, as a compound that inhibits Cdk4 and tubulin. Its IC50 value for Cdk4 inhibition is 0.47 μM and >50 μM for inhibition of Cdk1, Cdk2, Cdk6, Cdk9. Cink4T inhibits tubulin polymerization with an IC50 of 0.6 μM. Molecular modelling studies on Cink4T with Cdk4 and tubulin crystal structures lend support to these observations. Cancer cell cycle analyses confirm that Cink4T blocks cells at both G0/G1 and M phases as it should if it were to inhibit both Cdk4 and tubulin polymerization. Our results show, for the very first time, that virtual screening can be used to design novel inhibitors that can potently block two crucial phases of the cell division cycle.
- Sonawane, Vinay,Mohd Siddique, Mohd Usman,Jadav, Surender Singh,Sinha, Barij Nayan,Jayaprakash, Venkatesan,Chaudhuri, Bhabatosh
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p. 115 - 132
(2019/01/23)
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- Synthesis and antimicrobial activity of novel thienopyrimidine linked rhodanine derivatives
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This work presents the preparation of a new series of N-(substituted phenyl)-2-(4-oxo-5-(4-(thieno[2,3-d]-pyrimidin-4-yloxy)benzylidene)-2-thioxothiazolidin-3-yl)acetamide derivatives (8a-8l). A condensation reaction of thienopyrimidin-2-thioxothiazolidin
- Kerru, Nagaraju,Maddila, Surya Narayana,Maddila, Suresh,Sobhanapuram, Sreedhar,Jonnalagadda, Sreekantha B.
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- CYP enzymes, expressed within live human suspension cells, are superior to widely-used microsomal enzymes in identifying potent CYP1A1/CYP1B1 inhibitors: Identification of quinazolinones as CYP1A1/CYP1B1 inhibitors that efficiently reverse B[a]P toxicity and cisplatin resistance
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Microsomal cytochrome P450 (CYP) enzymes, isolated from recombinant bacterial/insect/yeast cells, are extensively used for drug metabolism studies. However, they may not always portray how a developmental drug would behave in human cells with intact intracellular transport mechanisms. This study emphasizes the usefulness of human HEK293 kidney cells, grown in ‘suspension’ for expression of CYPs, in finding potent CYP1A1/CYP1B1 inhibitors, as possible anticancer agents. With live cell-based assays, quinazolinones 9i/9b were found to be selective CYP1A1/CYP1B1 inhibitors with IC50 values of 30/21 nM, and > 150-fold selectivity over CYP2/3 enzymes, whereas they were far less active using commercially-available CYP1A1/CYP1B1 microsomal enzymes (IC50, >10/1.3–1.7 μM). Compound 9i prevented CYP1A1-mediated benzo[a]pyrene-toxicity in normal fibroblasts whereas 9b completely reversed cisplatin resistance in PC-3/prostate, COR-L23/lung, MIAPaCa-2/pancreatic and LS174T/colon cancer cells, underlining the human-cell-assays’ potential. Our results indicate that the most potent CYP1A1/CYP1B1 inhibitors would not have been identified if one had relied merely on microsomal enzymes.
- Sonawane, Vinay R.,Siddique, Mohd Usman Mohd,Gatchie, Linda,Williams, Ibidapo S.,Bharate, Sandip B.,Jayaprakash, Venkatesan,Sinha, Barij N.,Chaudhuri, Bhabatosh
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p. 177 - 194
(2019/02/27)
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- Discovery of Soft-Drug Topical Tool Modulators of Sphingosine-1-phosphate Receptor 1 (S1PR1)
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In order to study the role of S1PRs in inflammatory skin disease, S1PR modulators are dosed orally and topically in animal models of disease. The topical application of S1PR modulators in these models may, however, lead to systemic drug concentrations, wh
- Bell, Mark,Foley, David,Naylor, Claire,Wood, Gavin,Robinson, Colin,Riley, Jennifer,Epemolu, Ola,Ellis, Lucy,Scullion, Paul,Shishikura, Yoko,Osuna-Cabello, Maria,Ferguson, Liam,Pinto, Erika,Fletcher, Daniel,Katz, Elad,McLean, W. H. Irwin,Wyatt, Paul,Read, Kevin D,Woodland, Andrew
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p. 341 - 347
(2019/03/07)
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- Synthesis, Antimicrobial Evaluation, and Docking Studies of Substituted Acetylphenoxymethyl-triazolyl-N-phenylacetamides
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A series of molecules containing acetylphenoxymethyl, triazole, and N-phenylacetamide moieties were synthesized via the click chemistry approach. All the synthesized compounds were screened for their antimicrobial activities in vitro. The synthesized compounds 8a, 8b, 8m, and 8n showed better activities. We further performed exploratory docking studies to gain some insight regarding the molecular mechanism of antibacterial action of these compounds that could guide further structure-activity relationship (SAR) studies. We examined the interaction of the most active compound with DNA gyrase (pdb id:1KZN). Based on antimicrobial and docking studies, the compounds 8a, 8b, 8m, and 8n were identified as potential antimicrobial agents.
- Phatak, Pramod S.,Sathe, Bhaurao P.,Dhumal, Sambhaji T.,Rehman, Naziya N. M. A.,Dixit, Prashant P.,Khedkar, Vijay M.,Haval, Kishan P.
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- New: N -phenylacetamide-incorporated 1,2,3-triazoles: [Et3NH][OAc]-mediated efficient synthesis and biological evaluation
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A facile, highly efficient, and greener method for the synthesis of new 1,4-disubstituted-1,2,3-triazoles was conducted using [Et3NH][OAc] as a medium by the implementation of ultrasound irradiation via click chemistry, affording excellent yiel
- Akolkar, Satish V.,Nagargoje, Amol A.,Krishna, Vagolu S.,Sriram, Dharmarajan,Sangshetti, Jaiprakash N.,Damale, Manoj,Shingate, Bapurao B.
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p. 22080 - 22091
(2019/07/30)
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- Synthesis, antimicrobial activity, and molecular docking study of formylnaphthalenyloxymethyl-triazolyl-N-phenylacetamides
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In the present study, substituted formylnaphthalenyloxymethyl-triazolyl-N-phenylacetamide derivatives (6a–k) have been designed and synthesized employing click chemistry approach and evaluated for their in vitro antifungal and antibacterial activities. All the newly synthesized compounds were thoroughly characterized by 1H NMR, 13C NMR, and HRMS spectral techniques. Among the screened compounds, 6d, 6e, 6j, and 6k have shown good antifungal and antibacterial activities. Compound 6k has shown very effective antimicrobial activity. We further performed exploratory docking studies on microbial DNA gyrase to rationalize the in vitro biological data and to demonstrate the mechanism of antimicrobial activity. This is the first report to demonstrate the formylnaphthalenyloxymethyl, triazole, and N-phenylacetamide hybrids as potential antimicrobial agents.
- Muluk, Mahesh B.,Dhumal, Sambhaji T.,Phatak, Pramod S.,Rehman, Naziya N. M. A.,Dixit, Prashant P.,Choudhari, Prafulla B.,Mane, Ramrao A.,Haval, Kishan P.
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p. 2411 - 2418
(2019/07/31)
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- Novel series of acridone-1,2,3-triazole derivatives: microwave-assisted synthesis, DFT study and antibacterial activities
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Abstract: A series of novel acridones bearing a 1,2,3-triazole unit have been synthesized and characterized. The copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) was performed using both a conventional method and a microwave-assisted synthetic metho
- Aarjane, Mohammed,Slassi, Siham,Tazi, Bouchra,Maouloua, Mohamed,Amine, Amina
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- Design, synthesis, biological evaluation and molecular modeling study of new thieno[2,3-d]pyrimidines with anti-proliferative activity on pancreatic cancer cell lines
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Pancreatic cancer is one of the most challenging diseases with seven months only as median survival time due to its poor prognosis. Several enzymes are blamed for the progress of pancreatic cancer especially, platelet-derived growth factor receptors (PDGFRs), this in turn makes them promising targets for its treatment. In this study, twenty eight new compounds based on thieno[2,3-d]pyrimidine scaffold were synthesized as anti-pancreatic cancer agents mimicking the benzofuro[3,2-d]pyrimidine derivative, amuvatinib. Various linkers including amides, esters, ketones, urea and thiourea derivatives were utilized to study their effect on the anti-proliferative activity of these compounds. Most of the tested compounds revealed good cytotoxic activities against pancreatic carcinoma cell line PANC-1. Compound 9d showed the highest cytotoxicity with an IC50 value of 5.4 μM. Furthermore, 9d showed excellent platelet derived growth factor receptor (PDGFR-α) inhibitory activity, with IC50 value 0.155 μM. Docking study was carried out into PDGFR-α active site which showed comparable binding mode to that of FDA approved PDGFR-α inhibitor, imatinib. 3D-Quantitative structure activity relationship (QSAR) model was built up with five-featured pharmacophore which could be implemented for emerging effective lead structures. These compounds could serve as a new chemotype for discovering new agents for pancreatic cancer therapy.
- Salem, Mohamed S.H.,Abdel Aziz, Yasmine M.,Elgawish, Mohamed S.,Said, Mohamed M.,Abouzid, Khaled A.M.
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- Synthesis, bioevaluation and molecular docking study of new piperazine and amide linked dimeric 1,2,3-triazoles
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In search of more potent new antitubercular agents, a library of novel piperazine tethered dimeric 1,2,3-triazoles were designed by assembling 1,2,3-triazoles and piperazine in a single molecular architectural framework. The titled compounds (3a–m) were synthesized by 1,3-dipolar cycloaddition of 1,4-di(prop-2-yn-1-yl)piperazine (1) and various azides (2a–m) using click chemistry approach with good yields. All the synthesized compounds (3a–m) have been screened for their in vitro antitubercular, antifungal and antioxidant activities against their respective strains. Among them, 3b, 3d, and 3i have revealed promising antitubercular activity against Mycobacterium tuberculosis (Mtb) H37Rv with MIC 12.5 μg/mL. Molecular docking results provided well-clustered solutions to the mode of binding for these molecules into the active site of Mtb enoyl reductase (InhA). In addition to this, most of synthesized compounds were found to have potential antifungal as well as antioxidant activity.
- Deshmukh, Tejshri R.,Khare, Smita P.,Khedkar, Vijay M.,Krishna, Vagolu S.,Sangshetti, Jaiprakash N.,Shingate, Bapurao B.,Sriram, Dharmarajan
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supporting information
(2019/12/03)
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- THIAZOLOPYRIMIDINONE COMPOUNDS AND PREPARATION METHODS AND USE THEREOF
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The present invention provides structural details of a thiazolopyrimidinone compound, a preparation method thereof, and use thereof in the manufacture of a medicament for the treatment of central nervous system diseases.
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Paragraph 0038-0039; 0163-0164
(2018/06/15)
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- Design, synthesis, bioactivity, and computational studies of some morpholine-clubbed coumarinyl acetamide and cinnamide derivatives
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Abstract: The novel derivatives of morpholine-clubbed 3-substituted coumarinyl acetamide and cinnamide derivatives 5a–5j and 6a–6j have been synthesized via various 2-chloro-N-phenyl acetamide and cinnamoyl chloride derivatives, respectively. The required motif has been generated through Vilsmeier–Haack reaction on 4-hydroxycoumarin annelation of morpholine followed by imine formation and subsequently condensation with various 2-chloro-N-phenylacetamide and cinnamoyl chloride to furnish the desired molecule. The synthesized molecules were characterized by various spectroscopic methods viz IR, 1H NMR, 13C NMR. Their antimicrobial activities against various strains of bacteria and fungi have been evaluated, and computational studies have also been performed for all the newly synthesized analogs. Graphical Abstract: [Figure not available: see fulltext.].
- Chauhan, Prakashsingh M.,Thummar, Sandeep N.,Chikhalia, Kishor H.
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p. 1261 - 1277
(2018/05/22)
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- Structural optimization of N1-aryl-benzimidazoles for the discovery of new non-nucleoside reverse transcriptase inhibitors active against wild-type and mutant HIV-1 strains
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Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are recommended components of preferred combination antiretroviral therapies used for the treatment of human immunodeficiency virus (HIV) infection. These regimens are extremely effective in suppressing virus replication. Recently, our research group identified some N1-aryl-2-arylthioacetamido-benzimidazoles as a novel class of NNRTIs. In this research work we report the design, the synthesis and the structure–activity relationship studies of new compounds (20–34) in which some structural modifications have been introduced in order to investigate their effects on reverse transcriptase (RT) inhibition and to better define the features needed to increase the antiviral activity. Most of the new compounds proved to be highly effective in inhibiting both RT enzyme at nanomolar concentrations and HIV-1 replication in MT4 cells with minimal cytotoxicity. Among them, the most promising N1-aryl-2-arylthioacetamido-benzimidazoles and N1-aryl-2-aryloxyacetamido-benzimidazoles were also tested toward a panel of single- and double-mutants strain responsible for resistance to NNRTIs, showing in vitro antiviral activity toward single mutants L100I, K103N, Y181C, Y188L and E138K. The best results were observed for derivatives 29 and 33 active also against the double mutants F227L and V106A. Computational approaches were applied in order to rationalize the potency of the new synthesized inhibitors.
- Monforte, Anna Maria,De Luca, Laura,Buemi, Maria Rosa,Agharbaoui, Fatima E.,Pannecouque, Christophe,Ferro, Stefania
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p. 661 - 674
(2018/01/03)
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- Synthesis, antiproliferative evaluation, and structure–activity relationships of novel triazole–isoindoline hybrids bearing 3,4,5-trimethoxyphenyl moiety
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As an aspect of our ongoing research on developing novel antiproliferative agents, 31 new triazole–isoindoline hybrids bearing 3,4,5-trimethoxyphenyl moiety were synthesized and evaluated for their antiproliferative activity against four cancer cell lines (HepG2, HeLa, PC-3, and HCT116). Some compounds showed excellent potency, and compared to fluorouracil, the most promising compound 6s exhibited 5.8-, 4.3-, and 1.3- fold increase in activities against HeLa, HepG2, and PC-3 cell lines with IC50 values of 9.7, 10.7, and 16.8?μM, respectively. Moreover, structure–activity relationship studies indicated that a much shorter amide linkage and electron-withdrawing groups at phenyl ring of the acetamide fragment contribute to the antitumour activity.
- Li, Qiu,Chen, Peng,Yang, Haikui,Luo, Miaolan,You, Wenwei,Zhao, Peiliang
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p. 651 - 659
(2018/02/28)
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- Design, synthesis, and SAR of novel 2-glycinamide cyclohexyl sulfonamide derivatives against botrytis cinerea
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N-(2-trifluoromethyl-4-chlorophenyl)-2-oxocyclohexyl sulfonamide (chesulfamide) is in the limelight as a novel fungicide, and has fungicidal activity against Botrytis cinerea. For exploring more novel structures, 33 new compounds were synthesized by N-alkylation and acid–amine coupling reactions with chesulfamide as the core moiety, and their structures were characterized and established by 1H-NMR, 13C-NMR, MS, and elemental analysis. The structure of (1R,2S)-2-(2-(N-(4-chloro-2-trifluoromethylphenyl)sulfamoyl)-cyclohexylamino)-N-(2-trifluoromethylphenyl) acetamide (II-19) was defined by X-ray single crystal diffraction. The in vivo and in vitro fungicidal activities against B. cinerea were evaluated. The bioassay results of mycelial growth demonstrated that most compounds exhibited excellent inhibitory activity against B. cinerea at 50 μg mL?1, and 7 compounds showed lower EC50 values than boscalid (EC50 = 4.46 μg mL?1) against B. cinerea (CY-09). In cucumber pot experiment, the inhibitory rates of four compounds (II-4, II-5, II-12, and II-13) against B. cinerea were 90.48, 93.45, 92.86, and 91.07, which were better than cyprodinil (88.69%), the best performing of all controls. In tomato pot experiment, the control efficacy of two analogs (II-8 and II-15) were 87.98 and 87.97% at 200 μg mL?1, which were significantly higher than boscalid (78.10%). Most compounds have an excellent fungicidal effect on B. cinerea, with potential as a lead compound for developing new pesticides.
- Cai, Nan,Liu, Caixiu,Feng, Zhihui,Li, Xinghai,Qi, Zhiqiu,Ji, Mingshan,Qin, Peiwen,Ahmed, Wasim,Cui, Zining
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- Design, Synthesis and Computational Studies of Novel Carbazole N-phenylacetamide Hybrids as Potent Antibacterial, Anti-inflammatory, and Antioxidant Agents
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The present study deals with the synthesis of N-phenylacetamide-functionalized carbazole derivatives and their antibacterial, anti-inflammatory, and antioxidant assays. In vitro antibacterial studies of synthesized compounds shows prominent activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa. In addition, in silico molecular docking studies corroborated that the methyl substituent (3g), (3h), and (3i) showed promising activity with lower ?G (kcal/mol) values. This study envisages that these compounds can serve as a new leading template in the chemotherapy of various bacterial ailments.
- Pattanashetty, Shivarudrappa H.,Hosamani,Shettar, Arun Kashivishwanath,Mohammed Shafeeulla
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p. 1765 - 1774
(2018/07/25)
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- Biology-Oriented Drug Synthesis (BIODS) Approach towards Synthesis of Ciprofloxacin-Dithiocarbamate Hybrids and Their Antibacterial Potential both in Vitro and in Silico
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A novel series of ciprofloxacin-dithiocarbamate hybrids 7a?–?7l were designed, synthesized, and evaluated against Gram-positive and Gram-negative bacteria. A significant part of the title compounds showed considerable antibacterial activity against Gram-positive species. The most potent compound against Gram-positive bacteria was 2-chloro derivative 7h and the most potent derivative against Gram-negative bacteria was 3-chloro compound 7i. In?vitro antibacterial evaluation of compound 7h against clinically isolated bacteria methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA) showed that this compound acted better than ciprofloxacin against the latter bacteria. Docking study of compound 7h in the active site of S.?aureus DNA gyrase revealed that this ciprofloxacin-dithiocarbamate derivative interacted with the main components of the active site of the enzyme.
- Esfahani, Ensieh Nasli,Mohammadi-Khanaposhtani, Maryam,Rezaei, Zahra,Valizadeh, Yosef,Rajabnia, Ramazan,Bagheri, Meghdad,Bandarian, Fatemeh,Faramarzi, Mohammad Ali,Samadi, Nasrin,Amini, Mohammad Reza,Mahdavi, Mohammad,Larijani, Bagher
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- 1,3-dimethyl-7-substituted-quinazolinyl-2,4-diones, and synthesis method and application thereof
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The invention discloses 1,3-dimethyl-7-substituted-quinazolinyl-2,4-diones. The structural general formula of the compounds is disclosed in the specification, wherein R1 is hydrogen or ethyl; and R2 is a benzene ring, benzene ring derivative, heterocyclic ring or aliphatic hydrocarbon. Part of compounds have favorable inhibiting activities for Candida albicans, Aspergillus flavus, Torula histolytica and Aspergillus fumigatus. The compounds have obvious inhibiting activities for chitin synthetase, have favorable antibacterial effects, and can be used for preparing drugs for anti-pathogenic microorganisms.
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Paragraph 0056; 0057; 0058; 0059; 0060; 0069; 0070
(2017/07/31)
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- Potent, Selective, and Cell Active Protein Arginine Methyltransferase 5 (PRMT5) Inhibitor Developed by Structure-Based Virtual Screening and Hit Optimization
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PRMT5 plays important roles in diverse cellular processes and is upregulated in several human malignancies. Besides, PRMT5 has been validated as an anticancer target in mantle cell lymphoma. In this study, we found a potent and selective PRMT5 inhibitor by performing structure-based virtual screening and hit optimization. The identified compound 17 (IC50 = 0.33 μM) exhibited a broad selectivity against a panel of other methyltransferases. The direct binding of 17 to PRMT5 was validated by surface plasmon resonance experiments, with a Kd of 0.987 μM. Kinetic experiments indicated that 17 was a SAM competitive inhibitor other than the substrate. In addition, 17 showed selective antiproliferative effects against MV4-11 cells, and further studies indicated that the mechanism of cellular antitumor activity was due to the inhibition of PRMT5 mediated SmD3 methylation. 17 may represent a promising lead compound to understand more about PRMT5 and potentially assist the development of treatments for leukemia indications.
- Mao, Ruifeng,Shao, Jingwei,Zhu, Kongkai,Zhang, Yuanyuan,Ding, Hong,Zhang, Chenhua,Shi, Zhe,Jiang, Hualiang,Sun, Dequn,Duan, Wenhu,Luo, Cheng
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p. 6289 - 6304
(2017/08/02)
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- Synthesis, in?vitro evaluation and molecular docking studies of novel triazine-triazole derivatives as potential α-glucosidase inhibitors
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A novel series of triazine-triazole derivatives 7a–7m were synthesized, characterized by1H NMR and evaluated for their α-glucosidase inhibitory activity. All the synthesized compounds displayed potent α-glucosidase inhibitory activity with IC50range of 11.63?±?0.15 to 37.44?±?0.35?μM, when compared to the standard drug acarbose (IC50?=?817.38?±?6.27?μM). Among the series, compound 7i (IC50?=?11.63?±?0.15?μM) bearing 2,5-dichloro substitution at phenyl ring, represented the most potent α-glucosidase inhibitory activity. Molecular docking studies of the most active compounds with the homology modelled α-glucosidase were also performed to explore the possible inhibitory mechanism. Our studies shown that these triazine-triazole derivatives are a new class of α-glucosidase inhibitors.
- Wang, Guangcheng,Peng, Zhiyun,Wang, Jing,Li, Xin,Li, Juan
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p. 423 - 429
(2016/10/03)
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- Synthesis, molecular docking and α-glucosidase inhibition of 2-((5,6-diphenyl-1,2,4-triazin-3-yl)thio)-N-arylacetamides
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A novel series of 2-((5,6-diphenyl-1,2,4-triazin-3-yl)thio)-N-arylacetamides 5a–5q have been synthesized and evaluated for their α-glucosidase inhibitory activity. All newly synthesized compounds exhibited potent α-glucosidase inhibitory activity in the range of IC50?=?12.46?±?0.13–72.68?±?0.20?μM, when compared to the standard drug acarbose (IC50?=?817.38?±?6.27?μM). Among the series, compound 5j (12.46?±?0.13?μM) with strong electron-withdrawing nitro group on the arylacetamide moiety was identified as the most potent inhibitor of α-glucosidase. Molecular docking study was carried out to explore the binding interactions of these compounds with α-glucosidase. Our study identifies a novel series of potent α-glucosidase inhibitors for further investigation.
- Wang, Guangcheng,Li, Xin,Wang, Jing,Xie, Zhenzhen,Li, Luyao,Chen, Ming,Chen, Shan,Peng, Yaping
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p. 1115 - 1118
(2017/06/19)
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- Synthesis and antiviral evaluation of novel N-6 substituted adenosine analogues
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A series of adenosine analogues were synthesized and their biological evaluation was tested against Coxsackie virus B3 (CVB3) and Herpes simplex virus type 1(HSV-1) in HEp-2 cells. The hydrophobic constant, acute toxicity, carcinogenicity and mutagenicity were calculated. Analogues with piperazine derivatives 8b showed promising activities against CVB3 with a lower IC50value and higher selectivity index, their efficacy was better than that of the commercialized medicine, Ribavirin. These described adenosine analogues exhibit potent antiviral activities against several viruses, and offer new leads for further development.
- Hao, Youwu,Zhou, Gaohui,Wu, Wei,Zhang, Yang,Tao, Liming,Yao, Jianhua,Xu, Wenping
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p. 190 - 193
(2016/12/27)
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- Carbamylmethyl Mercaptoacetate Thioether: A Novel Scaffold for the Development of L1 Metallo-β-lactamase Inhibitors
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Given the clinical importance of metallo-β-lactamases (MβLs), a new scaffold, N-substituted carbamylmethyl mercaptoacetate thioether, was constructed. The obtained molecules 1-16 inhibited MβLs from all three subclasses, but preferentially L1 from subclass B3. Compound 9 with a p-carboxyphenyl substituent exhibited the broadest spectrum with at least 70% inhibition of enzymes from all subclasses at 100 μM, while compound 5 with a p-methylphenyl substituent was the most potent inhibitor of any individual enzyme, with 97% inhibition at 100 μM and an IC50 value of 0.41 μM against L1. Isothermal titration calorimetry assays corroborate findings from UV-vis spectrophotometric assays that the inhibition of L1 by 5 is dose-dependent. Docking studies suggest that the carboxyl group, the sulfide atom, and the carbonyl group of the carbamyl coordinate Zn2 in a chelating fashion. Using E. coli cells expressing L1, 6 and 8 were able to decrease cefazolin minimum inhibitory concentration 8-fold.
- Chang, Ya-Nan,Xiang, Yang,Zhang, Yue-Juan,Wang, Wen-Ming,Chen, Cheng,Oelschlaeger, Peter,Yang, Ke-Wu
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supporting information
p. 527 - 532
(2017/05/19)
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- Side chain-functionalized aniline-derived ursolic acid derivatives as multidrug resistance reversers that block the nuclear factor-kappa B (NF-κB) pathway and cell proliferation
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A series of inhibitors of NF-κB based on ursolic acid (UA) derivatives containing functionalized aniline or amide side chains were synthesized and evaluated for inhibition of NF-κB as well as their antitumor effects. These compounds exhibited significant inhibition activity toward NF-κB with IC50 values at micromolar concentrations in the NCI-H460 lung adenocarcinoma cell line. A docking study of the most active compound 5Y8 revealed key interactions between 5Y8 and the active site of NF-κB in which the functionalized amide moiety at the C-28 position and an ester group at the C-3 position were important for improving the activity. In particular, compound 5Y8 appeared to be the most potent compound against the NCI-H460 cell line, and displayed similar efficiency in drug-sensitive versus drug-resistant cancer cell lines, at least partly, by blocking the NF-κB signaling pathway and inducing apoptosis. Mechanistically, compound 5Y8 might trigger the apoptotic signaling pathway. Thus, the rational design of UA derivatives with functionalized aniline or amide side chains offers significant potential for the discovery of a new class of NF-κB inhibitors with the ability to induce apoptosis and reverse multidrug resistance in the NCI-H460 lung adenocarcinoma cell line.
- Huang, Ri-Zhen,Hua, Shi-Xian,Liao, Zhi-Xin,Huang, Xiao-Chao,Wang, Heng-Shan
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p. 1421 - 1434
(2017/07/25)
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- A convenient modified synthesis of 5-pyridinyl-1,3,4-thiadiazole-2-carboxamides
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A general one-pot procedure is developed for the synthesis of 5-pyridinyl-1,3,4-thiadiazole-2-carboxamides by the reaction of pyridine carboxaldehydes with oxamic acid thiohydrazides. (Figure Presented).
- Myannik,Yarovenko,Rodionova,Baryshnikova,Krayushkin
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p. 316 - 325
(2017/10/16)
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- Design and synthesis of novel 4'-demethyl-4-deoxypodophyllotoxin derivatives as potential anticancer agents
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A group of podophyllotoxin (PPT) derivatives (7a-j) were synthesized by conjugating aryloxyacetanilide moieties to the 4'-hydroxyl of 4'-demethyl-4-deoxypodophyllotoxin (DDPT), and their anticancer activity was evaluated. It was found that the most potent compound 7d inhibited the proliferation of three cancer cell lines with sub to low micromolar IC50 values. Furthermore, it was demonstrated that 7d induced cell cycle arrest in G2/M phase in MGC-803 cells, and regulated the expression of cell cycle check point proteins, such as cyclin A, cyclin B, CDK1, cdc25c, and p21. Finally, 4 mg/kg of 7d reduced the weights and volumes of HepG2 xenografts in mice. Our findings suggest that 7d might be a potential anticancer agent.
- Zhu, Xiong,Fu, Junjie,Tang, Yan,Gao, Yuan,Zhang, Shijin,Guo, Qinglong
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supporting information
p. 1360 - 1364
(2016/02/23)
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- Triazolylthioacetamide: A Valid Scaffold for the Development of New Delhi Metallo-β-Lactmase-1 (NDM-1) Inhibitors
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The metallo-β-lactamases (MβLs) cleave the β-lactam ring of β-lactam antibiotics, conferring resistance against these drugs to bacteria. Twenty-four triazolylthioacetamides were prepared and evaluated as inhibitors of representatives of the three subclasses of MβLs. All these compounds exhibited specific inhibitory activity against NDM-1 with an IC50 value range of 0.15-1.90 μM, but no activity against CcrA, ImiS, and L1 at inhibitor concentrations of up to 10 μM. Compounds 4d and 6c are partially mixed inhibitors with Ki values of 0.49 and 0.63 μM using cefazolin as the substrate. Structure-activity relationship studies reveal that replacement of hydrogen on the aromatic ring by chlorine, heteroatoms, or alkyl groups can affect bioactivity, while leaving the aromatic ring of the triazolylthiols unmodified maintains the inhibitory potency. Docking studies reveal that the typical potent inhibitors of NDM-1, 4d and 6c, form stable interactions in the active site of NDM-1, with the triazole bridging Zn1 and Zn2, and the amide interacting with Lys 211 (Lys224).
- Zhai, Le,Zhang, Yi-Lin,Kang, Joon S.,Oelschlaeger, Peter,Xiao, Lin,Nie, Sha-Sha,Yang, Ke-Wu
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supporting information
p. 413 - 417
(2016/05/19)
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- Mild and efficient palladium-catalyzed direct trifluoroethylation of aromatic systems by C-H activation
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The introduction of trifluoroalkyl groups into aromatic molecules is an important transformation in the field of organic and medicinal chemistry. However, the direct installation of fluoroalkyl groups onto aromatic molecules still represents a challenging and highly demanding synthetic task. Herein, a simple trifluoroethylation process that relies on the palladium-catalyzed C-H activation of aromatic compounds is described. With the utilization of a highly active trifluoroethyl(mesityl)iodonium salt, the developed catalytic method enables the first highly efficient and selective trifluoroethylation of aromatic compounds. The robust catalytic procedure provides the desired products in up to 95 % yield at 25 °C in 1.5 to 3 hours and tolerates a broad range of functional groups. The utilization of hypervalent reagents opens new synthetic possibilities for direct alkylations and fluoroalkylations in the field of transition-metal-catalyzed C-H activation.
- T?th, Balázs L.,Kovács, Szabolcs,Sályi, Gerg?,Novák, Zoltán
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supporting information
p. 1988 - 1992
(2016/02/18)
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- Synthesis, biological evaluation, in silico docking, and virtual ADME studies of 2-[2-Oxo-3-(arylimino)indolin-1-yl]-N-arylacetamides as potent anti-breast cancer agents
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A series of ten novel isatin analogs have been synthesized and screened for their in vitro anti-breast cancer activity against MCF-7 cell line using sulforhodamine-B assay method. All the tested compounds showed highly potent activity against MCF-7 cell line with especially four compounds exhibited demonstrative antiproliferative effects on MCF-7 breast cancer cell line compared to reference adramycin (doxorubicin) and GI 50 0.02 μM. Docking the synthesized compounds into the epidermal growth factor receptor, which is highly expressed in breast cancer, was employed to explore the possible interactions of these compounds with the receptor. Structure activity relationship as well as virtual ADME studies were carried out and a connection between activities, electronic and physicochemical properties of the target compounds was determined.
- Debnath, Biplab,Ganguly, Swastika
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p. 565 - 574
(2016/03/19)
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- Synthesis of Novel 6-Mercapto-12-phenethyl-quinazolino[3,4-a]quinazolinones
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Novel 6-mercapto-12-phenethyl-quinazolino[3,4-a]quinazolinone derivatives were synthesized through a user-friendly five-step reaction starting from isatoic anhydride. All products were characterized by IR,1H-NMR,13C-NMR spectroscopy, and chemical analysis. All of them were evaluated for their in vitro cytotoxic activity against two cell lines namely MOLT-4 (human lymphoblastic leukemia) and MCF-7 (human breast adenocarcinoma).
- Mohammadhosseini, Negar,Moradi, Shahram,Khoobi, Mehdi,Shafiee, Abbas
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p. 1595 - 1602
(2016/09/24)
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- Design, synthesis and biological evaluation of novel 3-alkylsulfanyl-4-amino-1,2,4-triazole derivatives
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Based on our previous work, a series of novel 3-alkylsulfanyl-4-amino-1,2,4-triazole derivatives were designed, synthesized and evaluated for their antiproliferative activities. The results indicated that some compounds possessed significant antiproliferative activities against four cancer cell lines, HepG2, HCT116, PC-3, and Hela. Particularly, the most promising compound 8d displayed 184-, 18-, and 17-fold improvement compared to fluorouracil in inhibiting HCT116, Hela and PC-3 cell proliferation with IC50values of 0.37, 2.94, and 31.31 μM, respectively. Most interestingly, the compound did not affect the normal human embryonic kidney cells, HEK-293. Moreover, mechanistic investigation showed that the representative compound 8d induced apoptosis and blocked cell cycle in G2/M phase in Hela cells in a dose-dependent manner. These findings suggest that compound 8d may have potential to be developed as a promising lead for the design of novel anticancer small-molecule drugs.
- Zhao, Pei-Liang,Chen, Peng,Li, Qiu,Hu, Meng-Jin,Diao, Peng-Cheng,Pan, En-Shan,You, Wen-Wei
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p. 3679 - 3683
(2016/07/21)
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- Synthesis and anti-leishmanial evaluation of 1-phenyl-2,3,4,9-tetrahydro-1H-β-carboline derivatives against Leishmania infantum
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In the present study, antileishmanial activity of sixteen novel series of tetrahydro-β-carboline derivatives against transgenic infrared fluorescent Leishmania infantum strain has been reported. Among these reported analogues, most of the compounds exhibited potent inhibition against both promastigote (IC50from 1.99?±?1.40 to 20.69?±?0.95?μM) and amastigote (IC50from 0.67?±?0.05 to 4.16?±?0.008?μM) forms of L.?infantum. Moreover, compound 7l, displayed most potent and selective inhibition of parasite amastigote form with IC500.67?±?0.05?μM, selectivity index >298.5 and was comparable with standard drug amphotericin B. From this study, a new class of tetrahydro-β-carboline derivatives with potent antileishmanial activity was identified and it needs further extensive study to optimize the lead molecules to win the battle against severe and neglected disease leishmaniasis.
- Ashok, Penta,Chander, Subhash,Tejería, Ana,García-Calvo, Laura,Bala?a-Fouce, Rafael,Murugesan, Sankaranarayanan
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p. 814 - 821
(2016/08/23)
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