An in silico study of bioactive compounds of Annona muricata in the design of ani-prostate cancer agent: MM/GBSA, pharmacophore modeling and ADMET parameters

Abstract

One of the most frequent diseases that affect and kill men globally is prostate cancer. Treatment for prostate cancer has become unpleasant and upsetting for individuals due to the resulting resistance, toxicity, and adverse effects of standard chemotherapies. Consequently, we report the identification of 263 bioactive chemicals in this investigation, some of which are responsible for known anti-cancer effect from Annona muricata using molecular docking, binding free energy estimates, induced-fit docking, gene enrichment analysis, molecular dynamic simulations, and ADMET predictions as examples of in silico approaches. The top 8 scoring compounds from a screening of 263 A. muricata samples revealed varying binding affinities between −9.854 and −8.179 kcal/mol towards the Human steroid 5′-reductase 2 enzyme. Amidst the top eight scoring compounds, annopentocin A, muricatetrocin A, and annohexocin had docking scores of −9.854, −9.337, and −9.337, respectively. The compounds such as annopentocin A communicated with amino acids of medical relevance such as GLU 57, ARG 227, TYR 91, TYR 98, LEU 111, SER 31 via H-bond and TRP 53, PHE 194, 118, 223, 219, 216, LEU 20, 17, 125, 224, 111, 167, ALA 117, TYR 33, 91, 98, 107, CYS 119, ILE 112 via Hydrophobic interaction. The compounds' capacity to impede protein activity was additionally confirmed by preferable docking scores in the induced-fit docking. Annopentocin A, Muricatetrocin A, Isoannonacinone, Annomuricin A and Muricatin C obeyed Lipinski's rule of 5 with favourable toxicity as well as pharmacokinetic prediction. However, there tend to be poor solubility profile and low GI absorption by the compounds which makes them more suitable for intravenous and topical administration than oral administration for optimal efficacy.