Two new phomanolide-type meroterpenoids from the endophytic fungi Plenodomus sp. IQ-2000.

Abstract

The genus Plenodomus remains relatively understudied, with limited reports regarding its specialized metabolites. In this study, the endophytic strain Plenodomus sp. IQ-2000, isolated from Tanacetum parthenium (L.) Schultz-Bip, was investigated following preliminary screenings that revealed a promising capacity to produce chemically diverse entities and inhibit human protein tyrosine phosphatase 1B (hPTP1B1-400). Using a strategy based on Feature-Based Molecular Networking (FBMN) integrated with the bioactivity of active fractions, five secondary metabolites (1-5) were prioritized and isolated. Their structures were elucidated through extensive NMR spectroscopy and high-resolution mass spectrometry (HRESIMS). Among the isolates, two undescribed phomanolide-type meroterpenoids, 7,8-epoxy-prephomanolide (1) and prephomanolide (2), are reported, whose absolute configuration were assigned via electronic circular dichroism (ECD) supported by time-dependent density functional theory (TDDFT) calculations. The isolation of 2 provides crucial experimental evidence for the previously hypothesized biosynthesis of this class of compounds. Compounds 2 and 3 exhibited moderate inhibitory potential against the evaluated target, with inhibition rates of 73.0 ± 3.5% and 51.5 ± 4.5% at 20 μg/mL, respectively. Notably, all isolated compounds are reported from the genus Plenodomus for the first time, expanding the known chemical space of this fungal genus.