The Design of Novel Protein Kinase Inhibitors Using the Naturally Occurring Isojacareubin Scaffold As A Lead

Abstract

Therapeutic areas for Protein Kinase inhibitors include cancer. A study has indicated that isojacareubin, a plant-derived natural product, inhibits Protein Kinase C. This study aimed to design in silico protein kinase inhibitors using isojacareubin as a molecular template. Virtual screening and de novo design were carried out during the study. A total of three hundred hits were produced from virtual screening using the best binding conformer of isojacareubin. Two hundred molecules were generated de novo from each seed structure of isojacareubin. Lipinski Rules compliant molecules were chosen from each study, and thus, were orally bioavailable. The binding affinities (pKd) of the Lipinski Rules compliant molecules produced ranged from 7.16 to 10.00. The molecules require further validation through in silco molecular dynamics and confirmed through in vitro assays.