New Phenylspirodrimanes from the Sponge-Associated Fungus Stachybotrys chartarum MUT 3308

Abstract

Two phenylspirodrimanes, never isolated before, stachybotrin J (1) and new stachybocin G (epi-stachybocin A) (2), along with the already reported stachybotrin I (3), stachybotrin H (4), stachybotrylactam (5), stachybotrylactam acetate (6), 2α-acetoxystachybotrylactam acetate (7), stachybotramide (8), chartarlactam B (9), and F1839-J (10) were isolated from the sponge-associated fungus Stachybotrys chartarum MUT 3308. Their structures were established based on extensive spectrometric (HRMS) and spectroscopic (1D and 2D NMR) analyses. Absolute configurations of the stereogenic centers of stachybotrin J (1), stachybocin G (2), and stachybotrin I (3), were determined by comparison of their experimental circular dichroism (CD) spectra with their time-dependent density functional theory (TD-DFT) circular dichroism (ECD) spectra. The putative structures of seventeen additional phenylspirodrimanes were proposed by analysis of their respective MS/MS spectra through a Feature-Based Molecular Networking approach. All the isolated compounds were evaluated for their cytotoxicity against five aggressive cancer cell lines (MP41, 786, 786R, CAL33, and CAL33RR), notably including two resistant human cancer cell lines (786R, CAL33RR), and compounds 5, 6, and 7 exhibited cytotoxicity with IC50 values in the range of 0.3−2.2 µM.

Phenylspirodrimane with Moderate Reversal Effect of Multidrug Resistance Isolated from the Deep-Sea Fungus Stachybotrys sp. 3A00409

“…They feature a common drimane-type sesquiterpene skeleton connected with a benzene ring through a spirofuran ring and show high structural diversity [19]. To date, over 120 compounds of this class, including monomeric and dimeric PSDs, have been discovered to derive from Stachybotrys [19][20][21][22][23]. These metabolites are designated as the most dominant group of mycotoxins in this genus [19,20,24].…”

“…These metabolites are designated as the most dominant group of mycotoxins in this genus [19,20,24]. PSDs can be further divided into three main classes: tetracyclic aromatic sesquiterpenoids with alcohol and/or aldehyde side chains, like stachybotrydial, pentacyclic aromatic sesquiterpenoids, such as stachybotrylactams and stachybotrylactones, and stachyflins with pentacyclic moiety including a cis-fused decalin [22,25]. They display diverse biological activities, including anticomplement, antiviral (HIV-1 and IAV) and anti-inflammatory activity, cytotoxicity, neuroprotective effects, tyrosine kinase inhibition, and tumor-related kinases inhibition [19].…”