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

Abstract

Two new phenylspirodrimanes, stachybotrins K and L (1 and 2), together with eight known analogues (3–10), were isolated from deep-sea-derived Stachybotrys sp. MCCC 3A00409. Their structures were determined by extensive NMR data and mass spectroscopic analysis. Absolute configurations of new compounds were determined through a comparison of their circular dichroism (CD) spectra with other reported compounds. The possible reversal effects of all compounds were assayed in the resistant cancer cell lines. Stachybotrysin B (8) can reverse multidrug resistance (MDR) in ABCB1-overexpression cells (KBv200, Hela/VCR) at the non-cytotoxic concentration. Doxorubicin accumulation assay and molecular-docking analysis reveal that the mechanism of its reversal MDR effect may be related to the increase in the intracellular concentration of substrate anticancer drugs.

Keywords

• deep-sea fungus
• <i>Stachybotrys</i>
• phenylspirodrimanes
• multidrug resistance (MDR)
• reversal MDR effects