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Letters in Drug Design & Discovery

Author(s): Shital M. Patil*, Shashikant V. Bhandari, Varsha A. Patil, Vrushali Randive and Indrani Mahadik

DOI: 10.2174/1570180820666230410083544

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Molecular Modeling of some 1,3,4-Oxadiazole Derivatives as EGFR Inhibitors for the Treatment of Cancer

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Abstract

Background: Cancer is a group of illnesses characterised by the impartial increase and unfolding of somatic cells. A variety of natural compounds, such as curcumin, zingiberine and their composites, and synthetic organic derivatives of imidazole, benzothiazole, oxadiazole, quinazoline etc., have been developed as anticancer agents. But many of these show various side effects, drug resilience, and toxicity to the normal cells of the host body. Therefore, there is still demand to develop new synthetic derivatives to improve their pharmacological profile.

Objective: The Aim of this study is to understand the binding mode and to check the drug likeliness of numerous 1,3,4-oxadiazole derivatives as EGFR inhibitors for the treatment of cancer. The objective of the study is to screen newly designed derivatives of 1,3,4-oxadiazole using molecular docking and ADMET studies as EGFR inhibitors.

Methods: In silico docking studies were performed using AutoDockVina software, and compounds were further studied for ADME and toxicity using SwissADME and pkCSM software, respectively.

Results: Considering the docking results, pharmacokinetic behaviour and toxicity profile, eight derivatives (derivatives 2,3,4,5,10,13,16, and 17) showed potential as EGFR inhibitors.

Conclusion: Compounds 2 and 3 showed the highest binding affinity in the pocket of EGFR and also displayed a better pharmacokinetic profile. Therefore, these derivatives can be used in the management of cancer and can be taken further for wet-lab studies.

Keywords: Anticancer, EGFR inhibitors, autoDockVina, swissADME, pkCSM, ADMET studies.

Graphical Abstract

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