Identification of potential edible spices as EGFR and EGFR mutant T790M/L858R inhibitors by structure-based virtual screening and molecular dynamics

Abstract

Epidermal growth factor receptor (EGFR) tyrosine kinases are overexpressed in several human cancers and could serve as a promising anti-cancer drug target. With this in view, the main aim of the present study was to identify spices having the potential to inhibit EGFR tyrosine kinase. The structure-based virtual screening of spice database consisting of 1439 compounds with EGFR tyrosine kinase (PDB ID: 3W32) was carried out using Glide. Top scored 18 hits (XP Glide Score ≥ −10.0 kcal/mol) was further docked with three EGFR tyrosine kinases and three EGFR T790M/L858R mutants using AutodockVina, followed by ADME filtration. The best three hits were further refined by Molecular Dynamics (MD) simulation and MM-GBSA-based binding energy calculation. The overall docking results of the selected hits with both EGFR and EGFR T790M/L858R were quite satisfactory and showed strong binding compared to the three coligands. Detailed MD analysis of CL_07, AC_11 and AS_49 also showed the stability of the protein-ligand complexes. Moreover, the hits were drug-like, and MM-GBSA binding free energy of CL_07 and AS_49 was established to be far better. AC_11 was found to be similar to the known inhibitor Gefitinib. Most of the potential hits are available in Allium cepa, CL_07 and AS_49 available in Curcuma longa and Allium sativum, respectively. Therefore, these three spices could be used as a potential therapeutic candidate against cancer caused by overexpression of EGFR after validation of the observations of this study in in-vitro experiments. Further extensive work is needed to improve the scaffolds CL_07, AC_11, AC_17, and AS_49 as potential anti-cancer drugs.

Communicated by Ramaswamy H. Sarma

Keywords:

• EGFR
• edible spices
• molecular docking
• molecular dynamics
• ADME
• MM-GBSA

Acknowledgement

The authors are thankful to Sri Rajat Ghosh, Assistant Professor, Dept. of Pharmacy, Tripura University, for providing Glide.

Data availability statement

The authors declare that all other data supporting the findings of the present study are available within the article as ‘Supplementary Information’

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

Not applicable.