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Computational Studies of Thiourea Derivatives as Anticancer Candidates through Inhibition of Sirtuin-1 (SIRT1)

1Faculty of Pharmacy, Universitas Bakti Tunas Husada, Tasikmalaya, West Java, Indonesia

2Department of Pharmacy, Faculty of Health Science, Universitas Perjuangan, Tasikmalaya 46115, West Java, Indonesia

3Faculty of Pharmacy, Universitas Indonesia, Depok, Indonesia

Received: 7 Dec 2021; Revised: 28 Feb 2022; Accepted: 8 Mar 2022; Published: 31 Mar 2022.
Open Access Copyright 2022 Jurnal Kimia Sains dan Aplikasi under http://creativecommons.org/licenses/by-sa/4.0.

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Abstract
Cancer is a disease that starts from the uncontrolled growth of abnormal cells in the organs or tissues of the body, which is the second leading cause of death in the world. One of the targets in discovering and developing anticancer drugs is Sirtuin-1. SIRT1 can act as a tumor suppressor or tumor promoter depending on its target in a particular signalling pathway or on particular cancer. This study aimed to study the interaction of a thiourea derivative with SIRT1 (PDB ID:4I5I) through its inhibition of histone deacetylase. Research has been carried out in silico with molecular docking (MGLTools.1.5.6) and molecular dynamics (Desmond 2019) of three thiourea derivatives to the receptor. In addition, pharmacokinetic parameters, toxicity, and selection of Lipinski's Rule of Five were also tested. Molecular docking results showed that compound b ([2-(methylcarbamothioylcarbamoyl)phenyl]benzoate) had the lowest ∆G value of −9.29 kcal/mol with a KI value of 0.156 µM compared to other thiourea derivatives and was proven by molecular dynamics tests for 30 ns and amino acids that play an active role in the interaction include the residue PheA:297. In terms of pharmacokinetics and toxicity, compound b is better than natural ligands. Compound b is predicted to be used as an anticancer candidate through further research.
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Keywords: molecular dynamics; cancer; molecular docking; sirtuin-1; thiourea
Funding: Bakti Tunas Husada College of Health Sciences; Universitas Perjuangan; Universitas Indonesia

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