Multitargeted molecular docking study of plant-derived natural products on phosphoinositide-3 kinase pathway components

Abstract

Phosphoinositide-3 kinase (PI3K) signaling pathway comprises of a cornucopia of protein molecules capable of regulating numerous cellular events, including cell survival, cell cycle regulation, angiogenesis, and apoptosis. Deregulation of PI3K downstream signaling is a phenomenon commonly seen in various types of cancer and also held responsible for poor prognosis and resistance to chemotherapy. Targeting PI3K signaling pathway has become a new and promising strategy in combating cancer. In the present study, PI3K signaling components PI3K, PDK1, Akt, and mTOR were chosen and 51 natural compounds along with 17 reference compounds were selected as ligand with the aid of PubMed published literature search. Ligands were docked to protein molecules by using Maestro 9.3 (Schrödinger Inc.). It was discovered in this study that compounds myricetin, quercetin, morin, luteolin, and emodin yielded excellent dock score with the proteins concluded with the help of docking free energy. The remarkable feature of these compounds are their various pharmacodynamics and pharmacokinetic characteristics, many of which are in accordance with the “Lipinski’s Rule of five”. The docking study carried out is an endeavor to portray the docking of these compounds with the proteins, to summarize the various Gscore, hydrogen bond, electrostatic bond, and to chart out various factors that are decisive for and also govern the protein–ligand interactions.