Design, and evaluation of in-silico anti-cancer activity of novel gefitinib analogues against 21 target proteins

Abstract

Over time, evidence suggests that numerous drugs have been discovered, and computer modelling, or the "In silico method", to understand how anti-cancer proteins interacted. Gefitinib, a quinazoline, inhibits the EGFR tyrosine kinase by attaching to its ATP-binding site. In order to find out how effective new gefitinib analogues are at targeting cancer, this study used molecular docking and ADMET analysis. In this study, the 21 anti-cancer target proteins were utilized to perform docking by using autodock tools. Twenty new analogues were created using ligand-based design, and frontier molecular orbital analysis revealed that the designed molecules are more reactive and softer. The majority of the designed molecules have higher binding affinities than gefitinib, according to the docking studies. Additionally, the analysis revealed that the compounds C-4, C-5, C-7, C-9, C-11, C-12, and C-14 have superior affinity to more than two targets. Docking experiments of the mutated target proteins with designed molecules demonstrate that many target proteins exhibit binding properties comparable to those of the unmutated proteins. According to the literature review on targets, these molecules may be helpful in the treatment of many cancers, including tumour growth, chronic myelogenous leukemia, chronic lymphocytic leukemia, acute myeloid leukemia, acute lymphoid leukemia, thyroid cancers, and salivary gland cancers. It was shown by the binding affinity, drug similarity score, and other ADMET experiments that the designed molecules will have more significant anti-cancer activity.