IN SILICO ASSESSMENT OF SOME BIOACTIVE MARINE XANTHONE DERIVATIVES AS POTENT INHIBITORS OF PI3Kγ BY MOLECULAR DOCKING APPROACH

Abstract

Protein PI3Kγ is a well-defined kinase target for cancer treatment that is important in regulating cell signaling, metabolism, growth, and cell proliferation. Our research aims to assess the anti-proliferation activity and mechanisms, the dual PI3K/mTOR binding affinity, and the mechanism of action of a series of bioactive xanthone derivatives from the marine. The performance of the AutoDock Vina software for predicting ligand-receptor binding affinities and poses of the compounds under study was first verified by available experimental data. Based on the validated AutoDock Vina parameters, a database of 169 marine xanthones were screened against the protein PI3Kγ. Natural compounds with lower docking scores (ΔG = -9,12 kcal/mol) than the positive control were subjected to MD simulation to evaluate structural changes compliant with the protein PI3Kγ. Structure and energy analyses showed that Austocystin L is highly stable within the active sites of the protein PI3Kγ. Austocystin L and Neocitreamicins I were suggested as agents against the protein PI3Kγ and to direct further biochemical experiments based on in silico calculations.