IN SILICO EVALUATION OF BINDING INTERACTION AND ADME PROPERTIES OF NOVEL 5-(THIOPHEN-2-YL)-1,3,4-OXADIAZOLE-2-AMINE DERIVATIVES AS ANTI-PROLIFERATIVE AGENTS

YOUSEF SABAH ALI; MONTHER FAISAL MAHDI; BASMA M. ABD RAZIK

doi:10.22159/ijap.2023v15i1.46488

Authors

YOUSEF SABAH ALI Department of Pharmaceutical Chemistry, College of Pharmacy, Mustansiriyah University, Baghdad, Iraq, Department of Pharmaceutical Chemistry, College of Pharmacy, Mustansiriyah University, Baghdad, Iraq https://orcid.org/0000-0002-8929-5786
MONTHER FAISAL MAHDI Department of Pharmaceutical Chemistry, College of Pharmacy, Mustansiriyah University, Baghdad, Iraq
BASMA M. ABD RAZIK Department of Pharmaceutical Chemistry, College of Pharmacy, Mustansiriyah University, Baghdad, Iraq

DOI:

https://doi.org/10.22159/ijap.2023v15i1.46488

Keywords:

Drug design, Molecular docking, Oxadiazole derivatives, Anti-proliferative

Abstract

Objective: The objective of this research was the virtual design of nine novel 1,3,4-oxadiazole derivatives and evaluating their antiproliferative activity as potential cyclin-dependent kinase 2 (CDK-2) inhibitors, which is a major component in cell cycle and proliferation.

Methods: CDK-2 structure, PDB ID, 2R3J, co-crystallized with ligand SCJ from protein data bank was chosen to be docked with a series of nine 5-(thiophen-2-yl)-1,3,4-oxadiazol-2-amine derivatives to evaluate their abilities as potential anti-proliferative agents using Glide software (Maestro 11.4) one of Schrodinger software (Schrodinger, 2018). In addition, the pharmacokinetic properties of these derivatives were evaluated using the Swiss-ADME web tool.

Results: Molecular modeling proposed that these 1,3,4-oxadiazole derivatives have powerful binding interaction with the active binding site of CDK-2 protein. In this article, two molecules have been observed as the most effective as they have docking scores of (-10.654 and-10.169 kcal/mol) respectively, whereas the binding score of the reference ligand was (-9.919 Kcal/mol) and most of the derivatives have fulfilled the Swiss-ADME parameters as potential orally active compounds.

Conclusion: Novel 1,3,4-oxadiazole derivatives had shown promising results to be considered as lead compounds for developing new anti-proliferative agents as two compounds (P-1 and P-5) exhibit better docking score at 2R3J active site than the reference ligand with further biological and pharmacological evaluation required.

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