Synthesis and Evaluation of A New Series of Thiazole Derivatives as Potential Antitumor Agents and MMP Inhibitors

Author(s): Zafer Asim Kaplancikli, Mehlika Dilek Altıntop*, Ozlem Atli, Belgin Sever, Merve Baysal, Halide Edip Temel, Fatih Demirci, Ahmet Ozdemir

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 17 , Issue 5 , 2017

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Graphical Abstract:


Background: In recent years, the relationship between overexpression of matrix metalloproteinases (MMPs) and tumor invasion/metastasis has prompted researchers to develop MMP inhibitors as anticancer drugs.

Objective: The aim of this study was to design and synthesize new thiazole-based anticancer agents targeting MMPs.

Method: New thiazole derivatives were synthesized and investigated for their cytotoxic effects on A549 human lung adenocarcinoma, MCF-7 human breast adenocarcinoma and NIH/3T3 mouse embryonic fibroblast cell lines using MTT assay. The potential inhibitory effects of the best candidates on gelatinases (MMP-2, MMP-9), and collagenases (MMP-1, MMP-8, MMP-13) were evaluated.

Results: Ethyl 2-[2-((4-amino-5-(phenoxymethyl)-4H-1,2,4-triazol-3-yl)thio)acetamido]-4-methylthiazole-5-carboxylate (3) was found to be the most promising anticancer agent against MCF-7 cell line due to its selective inhibitory effect on MCF-7 cells with an IC50 value of 20.6±0.3 μg/mL when compared with cisplatin (IC50= 35.31±0.51 μg/mL). Compound 3 also showed multiple MMP (MMP-1, MMP-8 and MMP-9) inhibitory activity (10.56±1.70, 20 and 7.28±1.49%, respectively).

Conclusion: The notable anticancer activity and selectivity of compound 3 on MCF-7 cell line can be attributed to multiple MMP inhibition potential.

Keywords: Thiazole, triazole, oxadiazole, anticancer activity, matrix metalloproteinase.

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Article Details

Year: 2017
Published on: 01 August, 2016
Page: [674 - 681]
Pages: 8
DOI: 10.2174/1871520616666160802113620
Price: $65

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