Design and Efficient Synthesis of Novel 4,5-Dimethylthiazole-Hydrazone Derivatives and their Anticancer Activity

Author(s): Asaf Evrim Evren*, Leyla Yurttaş, Büşra Ekselli, Onur Aksoy, Gülşen Akalin-Çiftçi

Journal Name: Letters in Drug Design & Discovery

Volume 18 , Issue 4 , 2021

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Graphical Abstract:


Background: Recently, researchers have been warning about the increased mortality of the various cancer types. Also, the lung adenocarcinoma and the glioma types are burning issues for world's health due to late or wrong diagnosis and/or insufficient treatment methods. For this purpose, our research group designed and synthesized novel 4,5-dimethyl thiazole-hydrazone derivatives which were tested against cancer and normal cell lines to understand the structureactivity relationship (SAR).

Methods: The lead compounds were obtained by reacting 2-(substituted aryl-2-ylmethylene) hydrazin-1-carbothioamide with 3-chloro-2-butanone derivatives. The structural elucidation of the compounds was performed by 1H-NMR, 13C-NMR, and LC/MS-IT-TOF spectral and elemental analyses. The synthesized compounds were tested in vitro for the anticancer activity against A549 human lung adenocarcinoma and C6 rat glioma cells and investigated for which pathway to induce cell death. Also, the docking study of the active compounds was achieved to understand the SAR.

Results: The targeted compounds (2a-2l) were synthesized successfully above 70% yields, and the analysis findings proved their purity. In general, the results of activity studies displayed significant effects against at least one cell line, except compounds 2e (indol-3-yl) and 2h (4-dimethylaminophenyl). Furthermore, compounds 2b and 2f displayed potential anticancer activity. With the help of molecular docking study, a potential selectivity of compound 2f was observed for type II protein kinase. On the other hand, compound 2b interacted with the active site nearly the same as Dasatinib. Therefore, these two compounds could be used as a base on developing selective anticancer drugs.

Conclusion: Pyridin-2-yl (2b) derivative was found to be a favorable molecule with high anticancer potency against C6 and A549 cell lines. Additionally, 1-naphthyl (2f) derivative was a worthy compound for potential selectivity. In future studies, it will be our priority to focus on developing derivatives of these two compounds (2b and 2f) and elucidate their mechanisms.

Keywords: Thiazole, hydrazone, A549, C6, apoptosis, anticancer activity.

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Article Details

Year: 2021
Published on: 22 October, 2020
Page: [372 - 386]
Pages: 15
DOI: 10.2174/1570180817999201022192937
Price: $65

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