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Thiazole-Based Thiosemicarbazones: Synthesis, Cytotoxicity Evaluation and Molecular Docking Study

Authors Gomha SM, Abdelhady HA, Hassain DZH, Abdelmonsef AH, El-Naggar M, Elaasser MM, Mahmoud HK

Received 20 November 2020

Accepted for publication 20 January 2021

Published 17 February 2021 Volume 2021:15 Pages 659—677


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 4

Editor who approved publication: Professor Manfred Ogris

Sobhi M Gomha,1,2 Hyam A Abdelhady,2 Doaa ZH Hassain,2 Aboubakr H Abdelmonsef,3 Mohamed El-Naggar,4 Mahmoud M Elaasser,5 Huda K Mahmoud2

1Chemistry Department, Faculty of Science, Islamic University in Almadinah Almonawara, Almadinah Almonawara, 42351, Saudi Arabia; 2Chemistry Department, Faculty of Science, University of Cairo, Giza, Egypt; 3Chemistry Department, Faculty of Science, South Valley University, Qena, 83523, Egypt; 4Chemistry Department, Faculty of Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates; 5The Regional Center for Mycology and Biotechnology, Al-Azhar University, Cairo, 11371, Egypt

Correspondence: Sobhi M Gomha Email
Aboubakr H Abdelmonsef Email

Introduction: Hybrid drug design has developed as a prime method for the development of novel anticancer therapies that can theoretically solve much of the pharmacokinetic disadvantages of traditional anticancer drugs. Thus a number of studies have indicated that thiazole-thiophene hybrids and their bis derivatives have important anticancer activity. Mammalian Rab7b protein is a member of the Rab GTPase protein family that controls the trafficking from endosomes to the TGN. Alteration in the Rab7b expression is implicated in differentiation of malignant cells, causing cancer.
Methods: 1-(4-Methyl-2-(2-(1-(thiophen-2-yl) ethylidene) hydrazinyl) thiazol-5-yl) ethanone was used as building block for synthesis of novel series of 5-(1-(2-(thiazol-2-yl) hydrazono) ethyl) thiazole derivatives. The bioactivities of the synthesized compounds were evaluated with respect to their antitumor activities against MCF-7 tumor cells using MTT assay. Computer-aided docking protocol was performed to study the possible molecular interactions between the newly synthetic thiazole compounds and the active binding site of the target protein Rab7b. Moreover, the in silico prediction of adsorption, distribution, metabolism, excretion (ADME) and toxicity (T) properties of synthesized compounds were carried out using admetSAR tool.
Results: The results obtained showed that derivatives 9 and 11b have promising activity (IC50 = 14.6 ± 0.8 and 28.3 ± 1.5 μM, respectively) compared to Cisplatin (IC50 = 13.6 ± 0.9 μM). The molecular docking analysis reveals that the synthesized compounds are predicted to be fit into the binding site of the target Rab7b. In summary, the synthetic thiazole compounds 1– 17 could be used as potent inhibitors as anticancer drugs.
Conclusion: Promising anticancer activity of compounds 9 and 11 compared with cisplatin reference drug suggests that these ligands may contribute as lead compounds in search of new anticancer agents to combat chemo-resistance.

Keywords: thiazoles, hydrazones, hydrazonoyl halides, docking, Rab7b, MCF-7

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