Title:Study on Molecular Anti-tumor Mechanism of 2-Thiohydantoin Derivative
based on Molecular Docking and Bioinformatic Analyses
Volume: 23
Issue: 6
Author(s): Ali AbdulWahid AbdulHussein Al-Shawi, Amr Ahmed El-Arabey, Dakhil Zughayir Mutlaq, Wafa Ali Eltayb, Marcello Iriti*Mohnad Abdalla*
Affiliation:
- Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, Milano, Italy
- National Interuniversity Consortium of Materials Science and Technology (INSTM), 50121 Firenze, Italy
- Pediatric Research Institute, Children's Hospital Affiliated to
Shandong University, Jinan, Shandong, 250022, China
Keywords:
2-Thiohydantoin derivatives, Flow cytometric analysis, AKT1, CDK2, Molecular docking, Bioinformatic analyses.
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.
