Title:3,4,5-Trisubstituted-1,2,4-triazole Derivatives as Antiproliferative Agents: Synthesis, In vitro Evaluation and Molecular Modelling
VOLUME: 17 ISSUE: 12
Author(s):Leyla Yurttaş*, Asaf Evrim Evren, Aslıhan Kubilay, Halide Edip Temel and Gülşen Akalın Çiftçi
Affiliation:Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Department of Analytical Chemistry,Faculty of Pharmacy, Anadolu University, Eskisehir 26470, Department of Biochemistry, Faculty of Pharmacy, Anadolu University, Eskisehir 26470, Department of Biochemistry, Faculty of Pharmacy, Anadolu University, Eskisehir 26470
Keywords:Triazole, thiazole, apoptosis, MMP-9, caspase-3, A549, molecular modelling.
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.
