Oxygenated Solanapyrone Analogs From Nigrospora sp. IQ-064, a Mangrove Associated Fungus

Two new oxygenated solanapyrone analogues, nigrosporapyrone E (1) and nigrosporapyrone F (2), were isolated from Nigrospora sp. strain IQ-064, a fungus associated with the bark of black mangrove (Avicennia germinans L.), along with seven known compounds. A targeted metabolomic strategy, on the basis of molecular networking and chemotaxonomic criteria, facilitated the isolation of these compounds. Their structures were characterized using HRESIMS and NMR spectroscopic analysis, whereas their relative configurations were established through NOE correlations. The absolute configuration of the new natural products was determined by comparison of experimental and calculated electronic circular dichroism (ECD) spectra, showing consistency with the recently reported natural product sphasolanapyrone A. Considering previous bioprospecting studies of this fungal strain, the isolated compounds were evaluated for their ability to inhibit human protein tyrosine phosphatase 1B (hPTP1B_1-400), a validated target for developing anti-diabetic drugs, as well as for their inhibitory activity against the pathogen Acinetobacter baumannii clinical isolate A564. However, no significant activity was observed in either bioassay. In addition, their ADME properties and probable bioactivity spectrum, predicted through SwissADME and PASS analysis, respectively, were analyzed to investigate alternative molecular targets within this compound family.