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Current Topics in Medicinal Chemistry

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ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

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Research Article

Study on Molecular Anti-tumor Mechanism of 2-Thiohydantoin Derivative based on Molecular Docking and Bioinformatic Analyses

Author(s): Ali AbdulWahid AbdulHussein Al-Shawi, Amr Ahmed El-Arabey, Dakhil Zughayir Mutlaq, Wafa Ali Eltayb, Marcello Iriti* and Mohnad Abdalla*

Volume 23, Issue 6, 2023

Published on: 27 January, 2023

Page: [440 - 452] Pages: 13

DOI: 10.2174/1568026623666230106121527

Price: $65

Abstract

Objective: Several methods for synthesizing 2-thiohydantoin derivatives have been devised and exploited, and they have found widespread application as antioxidants, antimicrobials, antivirals, and anticancer agents. As a result, we tried to understand the underlying processes of the 2- thiohydantoin derivative's anti-LIHC activity.

Methods: We predicted the anticancer mechanism of N-(4-oxo-5-(2-oxo-2-(p-tolylamino)ethyl)-3- phenyl-2-thioxoimidazolidin-1-yl)benzamide as a derivative of 2-thiohydantoin by utilizing molecular docking and molecular dynamic simulation. Furthermore, based on the results of molecular dynamic modelling, we employed bioinformatics to anticipate the immunotherapy of this molecule in the tumor microenvironment (TME) of Liver Hepatocellular Carcinoma (LIHC) patients. Next, we examined how this derivative affected proliferation, cell cycle progression, reactive oxygen species production, and apoptosis in HepG2 cancer cells.

Results: Substantially, our investigation revealed that the IC50 value was 2.448 μM and that it arrested the cell cycle of HepG2 in the S phase. Furthermore, molecular docking and dynamics studies revealed a worthy interaction of this compound with AKT1 and CDK2 proteins. Considerably, AKT1 and CDK2 have negative affinity energies of -10.4 kcal/mol and -9.6 kcal/mol, respectively. Several bioinformatic tools were used in this investigation to provide insight into the future clinical application of this derivative as a novel candidate to target immune cells such as macrophages, neutrophils, eosinophils, and CD8+ T cells.

Conclusion: The relevance of this 2-thiohydantoin derivative was demonstrated by our experimental tests, docking studies, and bioinformatics analysis, and it may be investigated as a lead molecule for anticancer medicines, notably as AKT1 and CKD2 inhibitors.

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