Antibacterial, Antifungal Chalcone Derivatives as EGFR Inhibitors-Molecular Docking and ADMET Studies

Hemalatha Sattu,Indira Rani Nerella,Saritha Jyostna Tangeda

doi:10.9734/jpri/2021/v33i45b32819

Abstract

Aim: In our earlier research, we have synthesized series of substituted 1-(2, 5-dimethyl thiophene-3yl)-(4-substituted phenyl)-2-propene-1-one derivatives and evaluated them for their anti-bacterial and antifungal activity. In recent years, chalcone derivatives are proved for their varied pharmacological effects ranging from antimicrobial activity to anti-cancer effects. In this study, we have hypothesized the efficiency of our earlier synthesized anti-bacterial and antifungal chalcone derivatives for their potential inhibition of epidermal growth factor receptor protein (EGFR), through molecular docking studies. Methodology: Molecular docking simulation studies are performed using the Glide XP module of Schrodinger Suite and ligand binding energies are also calculated. Results: Molecular docking studies of the selected compounds against EGFR revealed docking scores ranging from -6.746 (compound 5) to -5.681 (compound 3) and also provided insight into binding conformations of the ligands in the EGFR protein environment. Additionally, molecular property and Absorption, Distribution, Metabolism, and Excretion (ADME) predictor analysis is also performed for the dataset ligands, which further provided the probable explanation for the binding potentials. Conclusion: Among all the tested dataset ligands, compound 5 has shown the highest dock score (-6.746) with better ADME profiles. Binding energies in the protein-ligand interactions explain how fit the ligand binds with the target protein. Molecular docking studies of these anti-bacterial, antifungal chalcone derivatives provided deeper insights in understanding the probable conformations of these tested ligands in the EGFR protein environment.

Highlights

Two aromatic rings are linked by an aliphatic three-carbon chain with conjugated double bonds [1] in which derivatization mainly occurs through the substitutions on the aromatic rings resulting in a distinct variety of compounds
In silico studies on chalcones revealed that they have interaction with various cellular proteins which are responsible for causing cancer like CDK7, epidermal growth factor receptor protein (EGFR), etc
We have hypothesized the inhibitory potentials of the antibacterial, anti-fungal chalcone derivatives which were earlier designed and developed in our laboratory against EGFR protein [12]

Summary

Introduction

Two aromatic rings are linked by an aliphatic three-carbon chain with conjugated double bonds [1] in which derivatization mainly occurs through the substitutions on the aromatic rings resulting in a distinct variety of compounds. Chalcones possess distinct variety of pharmacological activities like anti-bacterial [2], anti-fungal [3], anti-inflammatory [4], anti-oxidant [5], anti-tuberculosis [6], anti-malarial [7], analgesic [8], anti-HIV [9], anti-tumor [10]. These chalcone derivatives exhibited anticancer activity on various drug-sensitive cell lines [11]. We have performed predictor analysis of molecular properties and ADME scores of the data set ligands

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Conclusion