Structure-based evaluation of Annona muricata bioactives for anticancer drug discovery: quantum chemical, molecular docking, and ADMET studies

Cancer remains a leading cause of mortality worldwide, necessitating the discovery of novel therapeutic agents with improved efficacy and safety profiles. The continuous search for effective and less toxic anticancer agents has led researchers to investigate natural compounds derived from plants. This study focuses on the bioactive compounds Annonacin, Quercetin, Coreximine, and Kaempferol from Soursop (Annona muricata), and their potential anticancer efficacy. Utilizing a structure-based drug discovery approach, we employed molecular docking studies to predict the interactions and binding affinities of these compounds with cancer-related proteins Human MUC16 SEA5 Domain (7SA9) and Mouse Double Minute 2 (4ZFI). Additionally, density functional theory (DFT) with the B3LYP functional and the 6–311* (d, p) basis set was used to perform geometry optimization and frequency calculations, providing detailed insights into the electronic properties, stability, and reactivity of the compounds. ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) studies were conducted to evaluate the pharmacokinetic and safety profiles of the compounds. From the ADMET result, coreximine is safest and Annonacin has toxicity risks. Quercetin and Kaempferol show intermediate potential but require optimization for solubility and toxicity mitigation. For the DFT result, Quercetin exhibits the strongest binding interactions (hydrogen bonds, π-stacking, and electrostatic contacts), followed by Coreximine’s high-affinity but hydrophobic-driven binding to 4ZFI, whereas Annonacin and Kaempferol show weaker, less-specific interactions. The finding identifies bioactive compounds from Annona muricata as a compound for developing new cancer drugs. The structure-based drug discovery framework can be applied to other medicinal plants, accelerating the identification of new natural product-based drugs.