Microbe-derived Bisindole Alkaloids with Anticancer Potential and Their Mechanisms: A Comprehensive Review

Bisindole alkaloids constitute a significant class of natural compounds distinguished by their characteristic bisindole structure and renowned for their anticancer properties. Over the past six decades, researchers have isolated 425 microorganism-derived bisindole alkaloids (MDBAs). Among them, 187 MDBAs have demonstrated anticancer properties against various in vitro cancer cell lines, primarily by impeding the cell cycle, restraining cell proliferation, and inducing apoptosis and autophagy. These effects are mediated through the regulation of key targets and signaling pathways such as HIF-1, MAPK, and PI3K/AKT/mTOR. This review provides a comprehensive examination of the sources, chemical diversity, and anticancer properties of these compounds. Furthermore, it offers a summary of the structure-activity relationship (SAR), druggability, and the mechanisms underlying MDBAs' anticancer effects. Ultimately, the aim of this paper is to furnish a thorough overview of the advancements in the investigation of microorganism-derived bisindole alkaloids for their continued development and utilization.