Publication: Design, synthesis and docking studies of new hydrazinyl-thiazole derivatives as anticancer and antimicrobial agents
Design, synthesis and docking studies of new hydrazinyl-thiazole derivatives as anticancer and antimicrobial agents
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Publisher DOI
10.1016/j.jscs.2022.101488
Date
2022-05-20
Type
Article
Authors
El-Naggar, Abeer M.
Zidan, Alaa
Elkaeed, Eslam B.
Taghour, Mohammed S.
Badawi, Waleed A.
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Publisher
Elsevier
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Source
https://www.sciencedirect.com/science/article/pii/S1319610322000709?via%3Dihub
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Abstract
Increase in the number of infections caused by pathogenic microbes in cancer patients has prompted the searcher to invest in the development of agents having dual anticancer and antimicrobial properties. The present study is concerned with synthesis and screening for anticancer and antimicrobial activity of a series of 5-hydrazinyl-2-(2-(1-(thien-2-yl)ethylidene)hydrazinyl)thiazole derivatives. The structure elucidation of the synthesized hydrazinyl thiazole derivatives was illustrated by spectroscopic and elemental analysis. All the newly synthesized compounds 5a-p were evaluated for in-vitro cytotoxic activity against breast carcinoma (MCF-7 cell line), hepatocellular carcinoma (HePG-2) and colorectal cancer (HCT-116) cell lines using MTT assay method. Compounds 5 g, 5h showed broad spectrum activity against three cancer cell lines with IC50 ranged from 3.81 to 11.34 µM in compared to the reference drug Roscovitine (IC50 = 9.32 to 13.82 µM), while compounds 5 l and 5 m were found to be more selective against HePG-2 and HCT-116 cell line (IC50 = 9.29 and 8.93 µM respectively) and compound 5j was more selective against HePG-2 and MCF-7 cell lines (IC50 = 6.73 and 10.87 µM respectively). The inhibitory activity of the most promising compounds was tested against the EGFR and ARO enzymes and were further tested for apoptosis and Annexin V/PI staining. The results of enzyme-based tests revealed that the tested compound 5j has a dual inhibitory effect on the EGFR and ARO enzymes with IC50 = 82.8 and 98.6 nM respectively in compared to the reference drugs Erlotinib and Letrozole (IC50 = 62.4 and 79 nM respectively). Furthermore, the majority of the tested hydrazinyl thiazole derivatives exhibited significant antimicrobial activity against the used pathogenic microbes species. Compounds 4b, 5h, 5j and 5 m exerted a good antibacterial and antifungal activity against all tested pathogenic microbes. Therefore, it was concluded that compounds 5 h, 5j and 5 m proved to possess dual anticancer and antimicrobial agent and may serves as a useful lead compounds in search for further modification or derivatization to give more potent and selective agents.
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Keywords
EGFR, Apoptosis, Cell cycle, Antibacterial, Hydrazinyl-thiazole, ARO, Anticancer
Citation
El-Naggar, A. M., Zidan, A., Elkaeed, E. B., Taghour, M. S., & Badawi, W. A. (2022). Design, synthesis and docking studies of new hydrazinyl-thiazole derivatives as anticancer and antimicrobial agents. Journal of Saudi Chemical Society, 26(4), 101488. https://doi.org/10.1016/j.jscs.2022.101488
Journal Title
Journal of Saudi Chemical Society
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Volume
26
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4
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© 2023 by the authors. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.