In silico screening of alkaloids as potential inhibitors of epidermal growth factor receptor

Abstract

The epidermal growth factor receptor (EGFR) belongs to the HER/erbB receptor tyrosine kinase (RTK) family, serving as a crucial target for cancer treatment. Anti-EGFR drugs, used as a primary treatment for patients with advanced EGFR gene mutations such as T790M, C797S, and L858R, have shown greater efficacy and safety compared to standard chemotherapy. This study aimed to screen alkaloid compounds with anticancer activity, extracted from the Selleckchem database that inhibit EGFR enzyme activity. The structure of the EGFR receptor was retrieved from the Protein Data Bank, whilst compounds were gathered from the alkaloids library within the Selleckchem database, with their structures downloaded from the PubChem database. Molecular docking was performed using Autodock Vina software. Lipinski’s rule of five was employed to distinguish between compounds with drug-like and non-drug-like properties. The pharmacokinetic parameters of potential compounds were evaluated using the pkCSM tool. Our research indicates that amongst the screened alkaloids, four compounds - peiminine, sanguinarine chloride, dauricine, and irinotecan - are the most promising inhibitors of the EGFR receptor for the treatment of lung cancer. These compounds exhibit high binding affinity for the active sites of EGFR, thus inhibiting its activity. All aforementioned compounds adhere to Lipinski’s rule and possess pharmacokinetic properties (absorption, distribution, metabolism, excretion, and toxicity - ADMET) that render them suitable for development into drugs.