Among microorganisms, endophytic fungi are the least studied, but they have attracted attention due to their high biological diversity and ability to produce novel and bioactive secondary metabolites to protect their host plant against biotic and abiotic stress. These compounds belong to different structural classes, such as alkaloids, peptides, terpenoids, polyketides, and steroids, which could present significant biological activities that are useful for pharmacological or medical applications. Recent reviews on endophytic fungi have mainly focused on the production of novel bioactive compounds. Here, we focus on compounds produced by endophytic fungi, reported with uncommon bioactive structures, establishing the neighbor net and diversity of endophytic fungi. The review includes compounds published from January 2015 to December 2020 that were catalogued as unprecedented, rare, uncommon, or possessing novel structural skeletons from more than 39 different genera, with Aspergillus and Penicillium being the most mentioned. They were reported as displaying cytotoxic, antitumor, antimicrobial, antiviral, or anti-inflammatory activity. The solid culture, using rice as a carbon source, was the most common medium utilized in the fermentation process when this type of compound was isolated.
Keywords: biological activity; endophytic fungi; uncommon secondary metabolites.