Bis-Indolyl Benzenoids, Hydroxypyrrolidine Derivatives and Other Constituents from Cultures of the Marine Sponge-Associated Fungus Aspergillus candidus KUFA0062
posted on 2018-10-11, 13:57authored bySuradet Buttachon, Alice A. Ramos, Ângela Inácio, Tida Dethoup, Luís Gales, Michael Lee, Paulo M. Costa, Artur M. S. Silva, Nazim Sekeroglu, Eduardo Rocha, Madalena M. M. Pinto, José A. Pereira, Anake Kijjoa
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), (3S, 6S)-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.
Funding
This work was partially supported through national funds provided by
the FCT/MCTES-Foundation for Science and Technology from the Minister of Science, Technology
and Higher Education (PIDDAC) and European Regional Development Fund (ERDF) through
the COMPETE—Programa Operacional Factores de Competitividade (POFC) programme, under the project
PTDC/MAR-BIO/4694/2014 (reference POCI-01-0145-FEDER-016790; Project 3599-Promover a Produção
Científica e Desenvolvimento Tecnológico e a Constituição de Redes Temáticas (3599-PPCDT)) in the framework of
the program PT2020 as well as by the project INNOVMAR-Innovation and Sustainability in the Management and
Exploitation of Marine Resources (reference NORTE-01-0145-FEDER-000035, within Research Line NOVELMAR),
supported by North Portugal Regional Operational Program (NORTE 2020), under the PORTUGAL 2020
Partnership Agreement, through the European Regional Development Fund (ERDF).
The following are available online at http://www.mdpi.com/1660-3397/16/4/119/s1,
Figure S1: Structures of palmitic acid, clionasterol and ergosterol-5,8-endoperoxide, isolated from the marine
sponge-associated fungus Aspergillus candidus KUFA0062, Figures S2–S35: 1D and 2D NMR spectra of isolated
compounds, Table S1: 1H NMR data of 2a–d (DMSO, 300.13 MHz), Table S2: 13C NMR data of 2a–d (DMSO,
75.3 MHz), Table S3: Comparison of 1H and 13C NMR data of 3 (DMSO, 300.13 and 75.4 MHz) and
2”-oxoasterriquinol D methyl ether (CDCl3
, 300 MHz), Table S4: 1H and 13C NMR data of 4 (kumbicin D)
(300.13 MHz and 75.4 MHz).