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A previously unreported bis -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 ), six bis -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 ), (3 S , 6 S )-3,6-dibenzylpiperazine-2,5-dione ( 6 ) and 4-(acetylamino) benzoic acid ( 7 ), from the cultures of the marine sponge-associated fungus Aspergillus candidus KUFA 0062. Compounds 1a , 2a-e , 3 , 4 , 5a-b , and 6 were tested for their antibacterial activity against Gram-positive and Gram-negative reference and multidrug-resistant strains isolated from the environment. Only 5a exhibited an inhibitory effect against S. aureus ATCC 29213 and E. faecalis ATCC29212 as well as both methicillin-resistant S. aureus (MRSA) and vancomycin-resistant enterococci (VRE) strains. Both 1a and 5a also reduced significant biofilm formation in E. coli ATCC 25922. Moreover, 2b and 5a revealed a synergistic effect with oxacillin against MRSA S. aureus 66/1 while 5a exhibited a strong synergistic effect with the antibiotic colistin against E. coli 1410/1. Compound 1a , 2a-e , 3 , 4 , 5a-b , and 6 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 1a , 2a , 2d , 4, and 6 , all the compounds showed cytotoxicity against all the cancer cell lines tested.

marine drugs

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