New Antimicrobial Cyclodepsipeptides from a Freshwater Fungus from the Sierra Madre Oriental in Mexico

The Sierra Madre Oriental (SMO) in Mexico is a complex, unexplored geological area with multiple habitats and unique physical, chemical, and biological features. A bioactive-guided study of the organic extract from a solid-state fermentation culture from a taxonomically unidentified fungus isolated from submerged wood in the waterfall "El Caracol", Nuevo Leon, at the SMO, led to the identification of three new cyclodepsipeptides (<b>1</b>-<b>3</b>) and the known Sch 217048 (<b>4</b>) and Sch 378161 (<b>5</b>). Structures of all compounds were elucidated by spectroscopic and spectrometric methods. The isolated compounds <b>4</b> and <b>5</b> showed antimicrobial activity against Gram-positive strains and the Gram-negative <i>Acinetobacter baumannii</i> ATCC 17978, including multidrug-resistant clinical strain A564. In addition, the compounds showed no toxic activity in the <i>Galleria mellonella</i> larvae model. Finally, the molecular networking analysis allowed us to annotate all the cyclodepsipeptides in the network. This is the first systematic chemical study of a fungus isolated from the SMO in Mexico.