3,4,5-Trisubstituted-1,2,4-triazole Derivatives as Antiproliferative Agents: Synthesis, In vitro Evaluation and Molecular Modelling

Author(s): Leyla Yurttaş*, Asaf Evrim Evren, Aslıhan Kubilay, Halide Edip Temel, Gülşen Akalın Çiftçi

Journal Name: Letters in Drug Design & Discovery

Volume 17 , Issue 12 , 2020

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Graphical Abstract:


Background: Cancer is the name given to various diseases that are mainly uncontrolled, related to cell growth and can affect various organs. Among them, lung cancer is the one, which, in its earliest stages, is difficult to diagnose, and it is asymptomatic until the disease progresses. Triazole ring is an important heterocyclic ring known with various pharmacological activities.

Objective: It is aimed to synthesize and characterize novel 1,2,4-triazole derivatives and screen them for in vitro antiproliferative activity and binding analysis through docking studies.

Method: In this study, we have synthesized new 2-[[5-[(4-aminophenoxy)methyl]-4-phenyl-4H- 1,2,4-triazol-3-yl]thio]-N-(substituted aryl)acetamide (5a-h) derivatives and investigated their anticancer activities against human lung cancer (A549) and mouse embryo fibroblast cell lines (NIH/3T3) by MTT, flow cytometric, caspase-3 and matrix metalloproteinase-9 (MMP-9) inhibition assays.

Results: Compounds 5f, 5g and 5h showed the highest cytotoxicity and caused significant apoptosis. These compounds inhibited MMP-9, slightly whereas they did not effect caspase-3.

Conclusion: 5f namely, N-(5-acetyl-4-methylthiazol-2-yl)-2-((5-((4-aminophenoxy)methyl)-4- phenyl-4H-1,2,4-triazol-3-yl)thio)acetamide exhibited as the most active compound with selective cytotoxicity and the highest MMP-9 inhibition. Besides, molecular modelling assessment was signified that antiproliferative activity of the compounds 5f, 5g and 5h was through a slight MMP-9 inhibition pathway.

Keywords: Triazole, thiazole, apoptosis, MMP-9, caspase-3, A549, molecular modelling.

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Article Details

Year: 2020
Published on: 19 November, 2020
Page: [1502 - 1515]
Pages: 14
DOI: 10.2174/1570180817999200712190831
Price: $65

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