Discovering new structural diversity from unexplored fungi

Discovery of anticancer drugs with high efficacy coupled with action at novel target sites is necessary to combat cancer. As part of a multidisciplinary project to identify anticancer leads from diverse natural product resources, our group has been studying fungi from different ecological habitats, including filamentous Ascomycota from terrestrial, freshwater, and symbiotic fungi (fungal endophytes), as a source of novel scaffolds for drug design and development. During the course of my research work, 56 bioactive compounds have been isolated and identified, with 30 of the isolated leads representing new chemical entities. Our lab relies on bioactivity-directed fractionation methodology for the isolation and purification of cytotoxic lead compounds from fungi, in which the bioassay results guide the purification processes. However, one of the inefficient outputs of utilizing this methodology is the re-isolation of previously known compounds, particularly mycotoxins. It is hypothesized that discovery of cytotoxic bioactive compounds with novel structures will be expedited by development and application of a dereplication methodology that has the capability to identify known compounds at the level of the crude extract. A dereplication methodology has been developed and implemented successfully for the identification of fungal secondary metabolites in crude culture extracts using a UPLC-PDA-HRMS-MS/MS method. Finally, the chemical diversity of the isolated compounds was analyzed through principal component analysis