Molecular docking analysis of podophyllotoxin derivatives in Sulawesi propolis as potent inhibitors of protein kinases

Abstract

Protein kinases are classified into several classes of enzymes that catalyze phosphorylation of proteins and thereby alter their substrate’s activity to interact with other proteins. Many of these enzymes are related to human cancer initiation and progression since many recent developments of small molecule kinase inhibitors has proven successful in diverse type of cancer clinically. Recent studies reported that propolis display variety of biological activities, including anticancer which indicated by the presence of podophyllotoxin derivatives, namely Sulawesins A and Sulawesins B. Podophyllotoxin is a natural compound which have been used as cancers and venereal wart therapies. Here, we conduct molecular docking analysis of mentioned compounds against a group of random-selected protein kinases. Present study aims to discover a most potent inhibitor of a protein kinase which desirably performing minimum side effects. The potentiality was explored by in silico approach through several software package programs, namely AutoDock Tools 1.5.6 to prepare the materials, AutoDock Vina to compute binding affinities of protein-ligand interactions and Ligplot to visualize the molecular interaction profile in 2D view. The molecular docking results depict that both Sulawesins A and B showed comparable inhibition potential towards Bruton’s tyrosine kinase (BTK) with docking score of -8.9 kcal/mol and -8.2 kcal/mol respectively, hence both are concluded as promising bioactive-compound candidates in the future for cancer therapies.