Curated phytochemicals of Annona muricata modulate proteins linked to type II diabetes mellitus: Molecular docking studies, ADMET and DFT calculation

Abstract

One of the medicinal herbs utilized in treating diabetes traditionally is Annona muricata. This work investigates the effect of phytochemicals from A. muricata on the therapeutically important protein targets associated with type II diabetes mellitus (T2DM) using a computational approach. Compounds (Phytochemicals) previously identified in A. muricata were docked against proteins of interest to find therapeutic hit compounds. The stability of the ligand-protein complexes was examined after selecting proteins that bind well with the discovered hits, and ADMET properties of the ligands were also predicted to determine their toxicity and drug-likeness. In addition to studying the compounds' softness, hardness, electron affinity, and electrostatic potential, the Schrödinger material science Jaguar fast engine was used to study their frontier molecular orbital (FMO). The targets aldose reductase (ALR), 11beta-hydroxysteroid dehydrogenase type 1 (11-HSD1), and diacylglycerol O-acyltransferase 1 (DGAT1) exhibited the highest binding affinities from the early screening of compounds against fifteen (15) proteins linked with T2DM. While eight (8) phenolic compounds of the plants had comparatively high docking scores with 11β-HSD1 and ALR, seven (7) acetogenins had good binding affinities with DGAT1. These top-scoring compounds exhibited considerable ADMET profiles. Additionally, the phenolic compounds that are considered as hits adhered to the Lipinski rule of 5 and can be thought of as potential drug candidates. Genistein and kaempferol are the most reactive ligands in terms of quantum mechanics. The information from this study could be used to create an alternative anti-diabetic drug with better efficacy.