Versiquinazolines L-Q, new polycyclic alkaloids from the marine-derived fungus Aspergillus versicolor

Further chemical examination of a coral-associated fungus Aspergillus versicolor LZD-14-1 by the PHLC-DAD detection resulted in the isolation of six new polycyclic alkaloids, namely versiquinazolines L-Q (1-6). Their structures were determined by extensive analyses of spectroscopic data, including quantum ECD calculation and X-ray single crystal diffraction for the assignment of absolute configurations. Versiquinazoline L bearing a d-Ala residue and versiquinazoline M containing an l-serine residue are rarely found in the fumiquinazoline-type alkaloids, while versiquinazoline P displayed an unusual scaffold with a spiro--lactone. Versiquinazolines P and Q exhibited significant inhibition against thioredoxin reductase (TrxR) with IC50 values of 13.6 +/- 0.6 and 12.2 +/- 0.7 M, which showed higher activity than the positive control curcumin (IC50 = 25 M). The weak cytotoxicity and potent inhibition toward TrxR suggested that versiquinazolines P and Q are potential for microenvironmental regulation of tumor progression and metastasis.