In silico study of 1-benzoyl-3-methylthiourea derivatives activity as epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor candidates

Abstract

Epidermal growth factor receptor (EGFR) is one of the important receptor tyrosine kinases (RTKs). The thiourea is widely used in drug discovery and development. Therefore, an in -silico study was carried out to investigate the ability of 1-benzoyl-3-methylthiourea derivatives to inhibit this receptor. The methods used include molecular docking to obtain the binding energy (Δ G) values (ArgusLab 4.0.1), drug- likeness study to ascertain the bioavailability level (MarvinSketch, Molinspiration), and determination of the toxicological properties of the carcinogenicity and mutagenicity (Toxtree). The results showed that 1-(3-Chlorobenzoyl)-3-methylthiourea (C -3) had the lowest binding energy (–9.28 kcal/mol). Furthermore, it showed that all the compounds and erlotinib satisfied the drug- likeness screening (Lipinski's rule of five, Veber's rule, Egan's rule) and that there was no genotoxic carcinogenicity. They showed the potential to become EGFR tyrosine kinase inhibitors, and this was confirmed through the dynamic molecular simulations carried out for 10 ns.