Synthesis, docking study, and in-vitro anti-cancer evaluation of new triazole derivatives of flufenamic acid

Background: Thiosemicarbazone, 1,2,3-triazole and their derivatives received great pharmaceutical importance due to their prominent biological activities. In the present study, the molecular hybrid thiosemicarbazone-1,2,3-triazoles derivatives were synthesized and screened for their antimicrobial activities. Methods: A series of thiosemicarbazone clubbed with 1,2,3-triazole derivatives were synthesized via click chemistry approach in good yields. The structures of synthesized compounds were assigned by their spectral data. The in vitro antimicrobial activity was performed by the agar well diffusion method. A molecular docking study was performed to identify the possible mode of action of synthesized derivatives. Results: The compounds 5d, 5h, 5i and 5k have exhibited excellent antimicrobial activities against both antibacterial and antifungal pathogens. The active thiosemicarbazone-1,2,3-triazole derivatives have shown excellent binding affinity towards DNA gyrase. Conclusion: The molecular hybrid thiosemicarbazone-1,2,3-triazole derivatives were synthesized. The newly synthesized compounds were evaluated for their antimicrobial activities. Few of the thiosemicarbazone-1,2,3-triazoles derivatives have exhibited good antimicrobial activities. They have been shown excellent binding affinity towards DNA gyrase.

Download Full-text

Synthesis, Electronic Structure and Anti-Cancer Activity of the Phenyl Substituted Pyrazolo[1,5-a][1,3,5]triazines

Current Organic Chemistry ◽

10.2174/1385272825666210607004536 ◽

2021 ◽

Vol 25 ◽

Author(s):

Evgenia S. Veligina ◽

Nataliya V. Obernikhina ◽

Stepan G. Pilyo ◽

Oleksiy D. Kachkovsky ◽

Volodymyr S. Brovarets

Keyword(s):

Electronic Transition ◽

Lone Electron Pair ◽

Electron Pair ◽

Anti Cancer ◽

Protein Molecules ◽

Biological Affinity ◽

Cancer Types ◽

Derivatives Of ◽

Cancer Activity

: Background: Synthesis of a series of 2-(dichloromethyl)pyrazolo[1,5- a][1,3,5]triazines was carried out and evaluated in vitro for their anticancer activity against a panel of 60 cell lines derived from nine cancer types. The joint quantum-chemical and experimental study of the influence of the extended πconjugated phenyl substituents on the electron structure of the pyrazolo[1,5-a][1,3,5]triazines as Pharmacophores were performed. It is shown that the decrease in the barriers to the rotation of phenyl substituents in compounds 1-7 possibly leads to an increase in the anti-cancer activity, which is in agreement with the change in the parameter biological affinity ϕ0. Analysis of the S0 → S1 electronic transitions (π→π*) of the pyrazolo[1,5-a][1,3,5]triazines shows that an increase in their intensity correlates with anti-cancer activity. Thus, the introduction of phenyl substituents increases the likelihood of investigated pyrazolo[1,5-a][1,3,5]triazines interacting with protein molecules (Biomolecule) by the π stacking mechanism. In both methyl and phenyl derivatives of pyrazolo[1,5-a][1,3,5]triazines, the second electronic transition includes the n-MO (the level of the lone electron pair in two-coordinated nitrogen atoms). The highest intensity of the η→π* electronic transition is observed in pyrazolo[1,5-a][1,3,5]triazine with pyridine residue, which does not exhibit anti-cancer activity, but exhibits antiviral activity [13]. It can be assumed that the possibility of the formation of [Pharmacophore-Biomolecule] complex by hydrogen bonding ([H-B]) mechanism with protein molecules increases.

Download Full-text

Synthesis of Some Novel Benzimidazole Derivatives as Anticancer Agent, and Evaluation for CDK2 Inhibition Activity

Medicinal Chemistry ◽

10.2174/1573406417666210304100830 ◽

2021 ◽

Vol 17 ◽

Author(s):

Rania Helmy Abd El-Hameed ◽

Samar Said Fatahala ◽

Amira Ibrahim Sayed

Keyword(s):

Cell Lines ◽

Docking Study ◽

Binding Pocket ◽

Kinase Assay ◽

Benzimidazole Derivatives ◽

Pharmacological Activities ◽

Anticancer Compounds ◽

Anti Cancer ◽

Hct 116

Background: Thiobezimidazoles reveal various pharmacological activities due to similarities with many natural and synthetic molecules, they can easily interact with biomolecules of living systems. Objective: A series of substituted 2-thiobezimidazoles has been synthesized .Twelve final compounds were screened for in vitro anti-cancer activities against sixty different cell-lines. Methods: The spectral data of the synthesized compounds were characterized. Docking study for active anticancer compounds and CDK2/CyclinA2 Kinase assay against standard reference; Imatinib were performed. Results: Two compounds (3c&3l) from the examined series revealed effective antitumor activity in vitro against two-cancer cell lines (Colon Cancer (HCT-116) and Renal Cancer (TK-10). The docking study of synthesized molecules discovered a requisite binding pose in CDK-ATP binding pocket. 3c &3l were promoted in the CDK2/CyclinA2 Kinase assay against standard reference Imatinib. Conclusion: Against all tested compounds ; two compounds 3c &3l were found active against two types of cell-lines.

Download Full-text

Molecular docking study on quercetin derivatives as inhibitors of PantothenateSynthetase (PanC) of Mycobacterium tuberculosis

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11i3.2529 ◽

2020 ◽

Vol 11 (3) ◽

pp. 3684-3690

Author(s):

Premalatha E ◽

Dineshraj R ◽

Iyanar Kannan ◽

Bhaarath KS ◽

Sharavanan TKV

Keyword(s):

3D Structure ◽

Acid Synthesis ◽

Docking Study ◽

Molecular Docking Study ◽

Quercetin Derivatives ◽

Pantothenate Synthetase ◽

Docking Tool ◽

Critical Components ◽

Derivatives Of

The anti-TB drugs currently in the use are insufficient to address these major health challenges. Hence, it is imperative to discover and develop new and efficient drugs against TB. The enzyme pantothenate synthetase (PS or PanC), necessary for the production of pantothenate (vitamin B5), critical components of fatty acid synthesis, when inhibited will in turn affect the cell wall synthesis of bacilli. In the present study, an attempt will be made to find the drug like molecules from quercetin derivatives prepared in silico to find out possible inhibitors of PanCof M. tuberculosis. The 3D structure of PanC was obtained from RCSB database and quercetin from ZINC database. The derivatives of quercetin were prepared and were docked initially with iGEMDOCK docking tool. The final docking was done in AutoDock vina software. The ADMET properties of the selected ligands were done in admetSAR online server tool. The present study revealed that four derivatives of quercetin has excellent binding with Pantothenate Synthetase (PanC) of M. tuberculosis. These derivatives can be taken for in vitro enzymatic assays for its inhibitory property in the search for new anti-TB drugs.

Download Full-text

Synthesis, Biological Activity, and Molecular Modeling Studies of Pyrazole and Triazole Derivatives as Selective COX-2 Inhibitors

Journal of Chemistry ◽

10.1155/2020/6393428 ◽

2020 ◽

Vol 2020 ◽

pp. 1-14 ◽

Cited By ~ 1

Author(s):

Mohyeddin Assali ◽

Murad Abualhasan ◽

Hadeel Sawaftah ◽

Mohammed Hawash ◽

Ahmed Mousa

Keyword(s):

Aromatic Ring ◽

Inhibitory Activity ◽

Click Reaction ◽

Docking Study ◽

The Other ◽

Synthetic Approach ◽

Triazole Derivatives ◽

Cox 2 ◽

Cox 2 Inhibitors

Series of diaryl-based pyrazole and triazole derivatives were designed and synthesized in a facile synthetic approach in order to produce selective COX-2 inhibitor. These series of derivatives were synthesized by different reactions like Vilsmeier–Haack reaction and click reaction. In vitro COX-1 and COX-2 inhibition studies showed that five compounds were potent and selective inhibitors of the COX-2 isozyme with IC50 values in 0.551–0.002 μM range. In the diarylpyrazole derivatives, compound 4b showed the best inhibitory activity against COX-2 with IC50 = 0.017 μM as one of the N-aromatic rings was substituted with sulfonamide and the other aromatic ring was unsubstituted. However, when the N-aromatic ring was substituted with sulfonamide and the other aromatic ring was substituted with sulfone (compound 4d), best COX-2 selectivity was achieved (IC50 = 0.098 μM, SI = 54.847). In the diaryltriazole derivatives, compound 15a showed the best inhibitory activity in comparison to all synthesized compounds including the reference celecoxib with IC50 = 0.002 μM and SI = 162.5 as it could better fit the extra hydrophobic pocket which is present in the COX-2 enzyme. Moreover, the docking study supports the obtained SAR data and binding similarities and differences on both isozymes.

Download Full-text

Synthesis of novel 1,2,3-triazole derivatives of isoniazid and their in vitro and in vivo antimycobacterial activity evaluation

European Journal of Medicinal Chemistry ◽

10.1016/j.ejmech.2014.05.005 ◽

2014 ◽

Vol 81 ◽

pp. 301-313 ◽

Cited By ~ 54

Author(s):

Deepak Kumar ◽

Beena ◽

Garima Khare ◽

Saqib Kidwai ◽

Anil K. Tyagi ◽

...

Keyword(s):

Antimycobacterial Activity ◽

Triazole Derivatives ◽

Activity Evaluation ◽

Derivatives Of

Download Full-text

Molecular Docking Study of Biologically Active Ligand and the Insights of Synthesis, Characterization and In Vitro Studies of Derivatives of β-tubulin Polymerization Inhibitor as Antigout Agent

Indian Journal of Science and Technology ◽

10.17485/ijst/2020/v13i07/149615 ◽

2020 ◽

Vol 13 (07) ◽

pp. 756-766

Author(s):

Vaishali H. Gaikwad

Keyword(s):

Docking Study ◽

Biologically Active ◽

Tubulin Polymerization ◽

Molecular Docking Study ◽

Polymerization Inhibitor ◽

Active Ligand ◽

Tubulin Polymerization Inhibitor ◽

Derivatives Of ◽

Β Tubulin

Download Full-text

Screening of phytochemicals from Golden apple of discord, Cydonia oblonga against the pTen and HBx using in silico-based tools.

10.21203/rs.3.rs-960905/v1 ◽

2021 ◽

Author(s):

Elhan Khan ◽

Iffat Zareen Ahmad

Keyword(s):

Hepatocellular Carcinoma ◽

In Silico ◽

Experimental Studies ◽

Docking Study ◽

Cydonia Oblonga ◽

Standard Drug ◽

Anti Cancer ◽

Anti Oxidant ◽

Inhibitory Potential ◽

Derivatives Of

Abstract Background Phytochemicals derived from Cydonia oblonga have been investigated for their anti-oxidant and anti-cancer activities in many cancer cells lines. The reported bioactive compounds are evaluated in-silico to develop a novel antagonist against pTEN and HBx to target hepatocellular carcinoma. Lower expression of pTEN or higher expression of HBx represents the progression of hepatocellular carcinoma (HCC). Objective This research is intended to identify the best candidate which interacts with our target proteins (pTEN and HBx) from the quince seeds by using computational methodologies. Materials and Methods The ternary structures of protein and phytochemicals reported in quince like derivatives of caffeoylquinic acid, kaempferol and quercetin, Chrysoeriol, Catechin and other compounds are retrieved from the online databanks. Druglikness analysis and ADMET profiling was done, followed by docking analysis. Lastly, molecular dynamics study was done to determine the complexes stability. Results Docking study revealed that CQA derivatives have the significant inhibitory potential of 3CQA and 5CQA with binding affinity of -7.53 and -7.49 against pTEN and -5.94 and -6.01 against HBx in comparison to the standard drug doxorubicin. The average RMSD and RMSF value for protein-ligand complexes were found quite stable comparative to the standard, while parameters like gyration and SASA supports the complexes having the significant binding and stability especially against pTEN. Conclusion The results obtained from the evaluation depict 3CQA and 5CQA shows best stability especially with the p10 protein target. Hence, these compounds have to be considered for detailed experimental studies to understand its biological function against HCC.

Download Full-text

Antioxidant, Antitumor and Bactericidal Activities of Ethyl Gallate Quinoxalines

Current Bioactive Compounds ◽

10.2174/1573407215666190318144105 ◽

2020 ◽

Vol 16 (6) ◽

pp. 900-910

Author(s):

Rafaely N. Lima ◽

Jaqueline R. Gonçalves ◽

Valdenizia R. Silva ◽

Luciano de S. Santos ◽

Daniel P. Bezerra ◽

...

Keyword(s):

Cell Lines ◽

Kinase Inhibitors ◽

Antioxidant Activities ◽

Hct116 Cell ◽

Docking Study ◽

Biological Potential ◽

Anti Cancer ◽

Bactericidal Activities ◽

Cancer Inhibition

Background: Quinoxaline, a fused heterocycle of benzene and pyrazine rings are becoming recognized as a potent class of anti-cancer compounds, such as, in a wide array of pharmacological activities. Methods: We evaluate the three gallate quinoxalines (G-A1, G-A2, and G-A3) as c-Met kinase inhibitors using a docking study, in vitro anticancer potential measurements, antioxidant and bactericidal activities. Results: The docking study showed hydrogen bond linkage of quinoxalines with amino acids at active site of c-Met kinase structures, indicating a possible cancer inhibition cell proliferation. Therefore, the three quinoxalines were analyzed against four in vitro cancer cell lines, and G-A1 demonstrated cytotoxicity against HL-60 and HCT116 cell lines (IC50= 9.55 and IC50= 16.67 μmol L-1, respectively). In HepG2 and MCF-7 cells, the IC50 were 22.48 and 33.42 μmol L-1, respectively. For G-A2 and G-A3, cytotoxic activity ranged from 61.22 to >101.21 μmol L-1. Potent antioxidant activities were also obtained for G-A2>G-A1>G-A3 (IC50= 4.5-8.4 μmol L-1 and AAI= 8.8-17.8). Six different Bacillius strains showed growth inhibition (11.33 to 13.33 mm) in the presence of quinoxaline G-A1 (500 μg). Conclusion: The present work showed the biological potential of quinoxalines G-A1, G-A2 and G-A3 in inhibiting four cancer cells proliferation, in addition to a very strong antioxidant activity.

Download Full-text