Kumbicin C

A previously unreportedbis-indolyl benzenoid, candidusin D (2e) and a new hydroxypyrrolidine alkaloid, preussin C (5b) were isolated together with fourteen previously described compounds: palmitic acid, clionasterol, ergosterol 5,8-endoperoxides, chrysophanic acid (1a), emodin (1b), sixbis-indolyl benzenoids including asterriquinol D dimethyl ether (2a), petromurin C (2b), kumbicin B (2c), kumbicin A (2d), 2″-oxoasterriquinol D methyl ether (3), kumbicin D (4), the hydroxypyrrolidine alkaloid preussin (5a), (3S, 6S)-3,6-dibenzylpiperazine-2,5-dione (6) and 4-(acetylamino) benzoic acid (7), from the cultures of the marine sponge-associated fungusAspergillus candidusKUFA 0062. Compounds1a,2a-e,3,4,5a-b, and6were tested for their antibacterial activity against Gram-positive and Gram-negative reference and multidrug-resistant strains isolated from the environment. Only5aexhibited an inhibitory effect againstS. aureusATCC 29213 andE. faecalisATCC29212 as well as both methicillin-resistantS. aureus(MRSA) and vancomycin-resistant enterococci (VRE) strains. Both1aand5aalso reduced significant biofilm formation inE. coliATCC 25922. Moreover,2band5arevealed a synergistic effect with oxacillin against MRSAS. aureus66/1 while5aexhibited a strong synergistic effect with the antibiotic colistin againstE. coli1410/1. Compound1a,2a-e,3,4,5a-b, and6were 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 for1a,2a,2d,4,and6, all the compounds showed cytotoxicity against all the cancer cell lines tested.