Fungal aromatic-bisabolane sesquiterpenoids—possible peptidylprolyl cis/trans isomerase (Pin1) inhibitors for cancer

Marine fungi have been proven as potential sources of natural metabolites with significant bioactivities that have not been sufficiently explored. This highlights the need for intensifying research to reach sustainable utilization of this huge factory of biodiverse metabolites. Aromatic-bisabolane sesquiterpenoids (ABSs) are a rare class of monocyclic sesquiterpenoids that have been reported from fungi, gorgonians, corals, sponges, and plants. These metabolites possessed significant bioactivities and intriguing chemical frameworks, indicating their substantial pharmaceutical and/or agricultural values. The current work covered the reported data on fungal ABSs, including their sources, isolation, structure characterization, and bioactivities. In addition, their Pin1 inhibitory potential as anticancer agents was assessed using in silico studies. Out of the compounds studied, 17 compounds showed docking scores which surpassed that of the reference ligand. Among these, three compounds demonstrated superior MM-GBSA binding free energies compared to the reference ligand. These three compounds underwent subsequent MD simulations, confirming the stability of their interactions. These findings suggested aspergoterpenin A, engyodontiumone I, (+)-1-hydroxyboivinianic acid, and methyl(S)-3-hydroxy-4-(2-hydroxy-6-methylheptan-2-yl) benzoate as possible new Pin1 inhibitors for further in vitro against prostate and esophageal cancer cells.