Computational study of the potential molecular target for antibreast cancer activity of limonoid derivatives from chisocheton SP

Abstract

Limonoid is a class of natural compounds that are originated from lemon and other citrus fruits. However, derivatives of limonoids are also produced in other plants, such as Chisocheton sp. Limonoids from Chisocheton sp. showed various biological activities, including anticancer. Nevertheless, the molecular target for anticancer activity of these compounds is still unclear. Many studies suggested nuclear receptors (NR) as the protein target for limonoids. In this study, we investigated the possible NR as a molecular target for limonoids from Chisocheton sp. using molecular docking and molecular dynamics (MD) simulation. The docking study was done on AutoDock Vina. Two out of 11 NR expressed in breast tissue, i.e., progesterone receptor (PR) and glucocorticoid receptor, was used as the most potential target for limonoids. The docking pose was further observed by MD simulation. Both receptors showed stable molecular interactions with limonoids, indicated with a low deviation of binding site residues. Interestingly, simulations of PR showed the alteration of Helix-12, which is one of the key factors to the antagonist action of the ligand. It is hoped that the findings could shed insight into the further molecular assay development of anticancer agents based on limonoids.