Molecular Binding Insights Into Folate Receptor and Acetogenins From Annona muricata L.: An In Silico Study

ABSTRACT Thirteen acetogenins were identified from the methanol extract of Annona muricata using LC‐MS analyses. The methanol extract showed antitumor activity against C33A, MDA‐MB‐231, A549, and ME180 cancer cells. Murihexocin B was isolated from the extract, identified by spectral methods and it showed an IC 50 value of 56.08 µg/mL against C33A cell lines. A molecular docking study was carried out against the folate receptor 4LRH, and the binding affinity of 13 acetogenins was determined. The binding energy is between −8.3 and −6.2 kcal/mol, and the acetogenins interacted with SER D 57, TYR D 60, PHE D 62, TYR D 64, ASP D 81, THR D 82, ARG D 103, and HIS D 135 amino acids present in the active site by means of hydrogen bonding and hydrophobic interactions and ultimately contributed to high stability of binding between acetogenins and the folic acid receptors. The stability and dependability of murihexocin B binding were evaluated using a 100 ns molecular dynamics simulation. With minimal deviation and fluctuation, it revealed no discernible unfolding of the binding complexes and confirms the strong interactions. According to an in silico ADMET study, these compounds have above 90% PPB permeability, positive blood‐brain barrier penetration, low bioavailability, and less toxicity.