Computational Assessment of Bioactive Compounds from Holoptelea integrifolia (Roxb). Planch against breast cancer using Molecular Docking and ADMET analysis

Introduction: Breast cancer continues to be among the major causes of deaths globally, calling for the immediate creation of new, safe, and multitarget drugs. In the current research, the anticancer activity of Holoptelea integrifolia (Roxb.) Planch against breast cancer has been assessed using docking and ADMET analysis. The integrated approach has been applied for the discovery of phytochemicals with anticancer activity, identification of their target molecules and assessment of pharmacokinetic and drug-like properties.

Methods: The in-silico screening of phytochemicals derived from the of Holoptelea integrifolia for EGFR tyrosine kinase. Firstly, the drug-likeness and ADMET profile of the phytochemicals was determined through the SwissADME (https://www.swissadme.ch/). Thereafter, phytochemicals that showed promising drug-likeness and least-toxic properties were used for molecular docking using maestro 13.7.125 (Schrodinger Ltd. USA) software to explore their binding properties towards the EGFR receptor (PDB ID: 4HJO) available from the RCSB protein data bank (https://www.rcsb.org/)

Results: This work evaluated the probable mechanism of phytochemicals for its activity against breast cancer. Upon screening of total 12 Compounds for drug likeness and its ADMET profiling, four compounds showed the within the acceptable limit. Further, docking of selected four compounds revealed stigmasterol having the best binding interactions against the EGFR receptor with a docking score of -4.355 Kcal/mol.

Conclusion: The findings of the study provides a computational framework for understanding the molecular interaction between the phytochemicals from Holoptelea integrifolia against EGFR, thereby supporting their potential lead molecules for the effective therapeutic agents against breast cancer.