Mohamed A Tammam, Islam El-Awaad, Adnane Aouidate, Reham Hassan Mekky, Amr El-Demerdash
Covering: 2005-2025Pyrrocidines and hirsutellones are a fascinating class of fungal natural products that possess an intricate chemical structure characterized by a distinctive macrocyclic ring fused to a decahydrofluorene core. Known for their complex architectures as PKS-NRPS hybrids, these metabolites are isolated from various fungi and have attracted significant attention due to their potent pharmacological properties, including antimicrobial, antifungal, and anticancer effects. This review article aims to shed light on the structural diversities of 52 fungal-derived pyrrocidines and hirsutellones reported over the period of 2005-2025, providing insights into their chemistry, biosynthetic origins, pharmacokinetic profiles, and structure-activity relationships (SARs). Furthermore, we critically evaluate their promising therapeutic potential, highlighting the opportunities they present for modern drug discovery and development.