Bis-Indolyl Benzenoids, Hydroxypyrrolidine Derivatives and Other Constituents from Cultures of the Marine Sponge-Associated Fungus Aspergillus candidus KUFA0062

Abstract

A previously unreported <i>bis</i>-indolyl benzenoid, candidusin D (<b>2e</b>) and a new hydroxypyrrolidine alkaloid, preussin C (<b>5b</b>) were isolated together with fourteen previously described compounds: palmitic acid, clionasterol, ergosterol 5,8-endoperoxides, chrysophanic acid (<b>1a</b>), emodin (<b>1b</b>), six <i>bis</i>-indolyl benzenoids including asterriquinol D dimethyl ether (<b>2a</b>), petromurin C (<b>2b</b>), kumbicin B (<b>2c</b>), kumbicin A (<b>2d</b>), 2″-oxoasterriquinol D methyl ether (<b>3</b>), kumbicin D (<b>4</b>), the hydroxypyrrolidine alkaloid preussin (<b>5a</b>), (3<i>S</i>, 6<i>S</i>)-3,6-dibenzylpiperazine-2,5-dione (<b>6</b>) and 4-(acetylamino) benzoic acid (<b>7</b>), from the cultures of the marine sponge-associated fungus <i>Aspergillus candidus</i> KUFA 0062. Compounds <b>1a</b>, <b>2a-e</b>, <b>3</b>, <b>4</b>, <b>5a-b</b>, and <b>6</b> were tested for their antibacterial activity against Gram-positive and Gram-negative reference and multidrug-resistant strains isolated from the environment. Only <b>5a</b> exhibited an inhibitory effect against <i>S. aureus</i> ATCC 29213 and <i>E. faecalis</i> ATCC29212 as well as both methicillin-resistant <i>S. aureus</i> (MRSA) and vancomycin-resistant enterococci (VRE) strains. Both <b>1a</b> and <b>5a</b> also reduced significant biofilm formation in <i>E. coli</i> ATCC 25922. Moreover, <b>2b</b> and <b>5a</b> revealed a synergistic effect with oxacillin against MRSA <i>S. aureus</i> 66/1 while <b>5a</b> exhibited a strong synergistic effect with the antibiotic colistin against <i>E. coli</i> 1410/1. Compound <b>1a</b>, <b>2a-e</b>, <b>3</b>, <b>4</b>, <b>5a-b</b>, and <b>6</b> were also tested, together with the crude extract, for cytotoxic effect against eight cancer cell lines: HepG2, HT29, HCT116, A549, A 375, MCF-7, U-251, and T98G. Except for <b>1a</b>, <b>2a</b>, <b>2d</b>, <b>4,</b> and <b>6</b>, all the compounds showed cytotoxicity against all the cancer cell lines tested.