Mycotoxins as inhibitors of protein tyrosine phosphatases from the deep-sea-derived fungus Aspergillus puniceus SCSIO z021

Abstract

Nine new xanthone-type and anthraquinone-type mycotoxins including austocystins J-N (1–5), 7-chloro versicolorin A (6), 3′-hydroxy-8-O-methyl versicolorin B (7), 8-O-methyl versiconol (8) and 2′,3′-dihydroxy versiconol (9), together with 17 known analogues (10–26) were isolated from an extract of the deep-sea-derived fungus Aspergillus puniceus SCSIO z021. Their structures were elucidated by detailed analysis of spectroscopic data, and their absolute configurations were further determined by quantum chemical calculations of ECD spectra or comparison of the experimental ECD spectra. Eleven hydrogenated austocystins were synthesized from 1–2, 10–15 and 17 by catalytic hydrogenation for bioactivities evaluation. Totally, 18 of the all 37 compounds showed strong toxicity against brine shrimps or Vero cell, and the toxicity of 8-O-methyldemethylsterigmatocystin (18) (LC50 = 0.020 µM) against brine shrimps was higher than those of three positive controls. In addition, 22 of the isolated compounds also exhibited significant inhibitory activity against seven different protein tyrosine phosphatases (PTPs), among them austocystin H (15) and methyl-averantin (24) were the most potent inhibitors with IC50 values of 0.20–3.0 µM. Their structure-bioactivity relationship was also discussed.