In Vitro and In Silico Anticyclooxygenase and Antitopoisomerase Activity of Anonna cherimola Ent-Kaurenes

Annona cherimola is noted for its bioactive compounds, particularly diterpenes called ent-kaurenes, which exhibit various biological activities. This study focused on evaluating the ability of ent-kaurenes from Annona cherimola to inhibit cyclooxygenase (COX) and topoisomerase (TOP) enzymes. Researchers used solvent-free lipophilic eluates (SFLEs) from the plant in enzymatic assays and a yeast model. The major compounds in SFLE were identified using gas chromatography–mass spectrometry (GC-MS), and in silico studies explored their inhibition mechanisms. SFLE showed significant inhibition of COX-II (95.44%) and COX-I (75.78%) enzymes and fully inhibited the yeast strain. The effectiveness of inhibition is attributed to the compounds’ structural diversity, lipophilicity, and molecular weight. Two main compounds, kauran-16-ol and isopimaral, were identified, with in silico results suggesting that they inhibit COX-II by blocking peroxidase activity and COX-I by interacting with the membrane-binding region. Additionally, these compounds allosterically and synergistically inhibit TOP-II and potentially sensitize cancer cells by interacting with key amino acids. This research is the first to identify and evaluate kauran-16-ol and isopimaral in silico, suggesting their potential as anti-inflammatory and anticancer agents.