In silico design, anti-proliferative activity modeling, molecular docking and pharmacokinetic properties prediction of some non-small cell lung cancer (NSCLC) therapeutic agents

Abstract

Lung cancer remains the leading and deadly type of cancers worldwide. It was estimated to account for about 25% of the 7 million people that died as a result of cancer-related illness every year in the world. In silico/structure-based approach was used to design nine (9) new non-small cell lung cancer (NSCLC) drugs using molecule 22 (as template for the design) identified with the best binding affinity previously reported in our work. The anti- proliferative activity of these newly designed NSCLC drugs was predicted using the best model reported in our previous work and found have better anti-proliferative activities than that of the hit compound with antiproliferative activity of 6.069 except for compounds SCD 3, SCD 6 and SCD 7 respectively. Molecular docking was studied to investigate and explore the mode of binding of these newly designed NSCLC drugs with the active site of epidermal growth factor receptor (EGFR) kinase enzyme and found have better affinities
(between 10.5 kcal/mole to 11.0 kcal/mole) than the template (molecule 22) with a binding affinity of 10.4 kcal/mole and the control gefitinib with a binding affinity of - 8.0 kcal/mole, respectively. None of them was found to have more than one violation of the filtering criterion used in this study which confirms their oral bioavailability with good ADMET properties. The modeled anti-proliferative activities and binding affinities of these newly designed NSCLC drugs were found to be better than that of the template (Molecule 22) and the control (Gefitinib) used in this study. They were
also found to be non-toxic with good pharmacokinetic properties.