Bioprospection of Cytotoxic Compounds in Fungal Strains Recovered from Sediments of the Brazilian Coast

Abstract

The cytotoxic activities of extracts (50 μg/ml) from 48 fungal strains, recovered from sediments of Pecém's offshore port terminal (Northeast coast of Brazil), against HCT-116 colon cancer cell lines were investigated. The most promising extract was obtained from strain BRF082, identified as Dichotomomyces cejpii by phylogenetic analyses of partial RPB2 gene sequence. Thus, it was selected for bioassay-guided isolation of the cytotoxic compounds. Large-scale fermentation of BRF082 in potato dextrose broth, followed by chromatographic purification of the bioactive fractions from the liquid medium, yielded gliotoxin (4) and its derivatives acetylgliotoxin G (3), bis(dethio)bis(methylsulfanyl)gliotoxin (1), acetylgliotoxin (5), 6-acetylbis(dethio)bis(methylsulfanyl)gliotoxin (2), besides the quinazolinone alkaloid fiscalin B. All isolated compounds were tested for their cytotoxicities against the tumor cell lines HCT-116, revealing 4 and 3 as the most cytotoxic ones (IC50 0.41 and 1.06 μg/ml, resp.).

Aspergillus is monophyletic: Evidence from multiple gene phylogenies and extrolites profiles

“…A. cejpii has been shown to produce gliotoxins and fiscalin B in common with A. fumigatus and A. fischeri (Varga et al., 2007, Frisvad and Larsen, 2015, Harms et al., 2015a, Rodrigues et al., 2015, Fan et al., 2016), xanthocillins (Kitahara and Endo, 1981, Harms et al., 2015b) in common with A. fumigatus (Zuck et al. 2011), showing several chemical similarities between A. cejpii with its phylogenetic sister group section Fumigati .…”

Marine natural products

“…320 This fatty acid inhibited growth of MCF-7 cells and down-regulated the lipogenic enzymes acetyl CoA carboxylase (ACC) and fatty acid synthase (FAS). 321 Acetylgliotoxin G 322 543 was obtained for the rst time as a MNP as was the known synthetic open-chain hemisuccinimide 544, 323 (Penicillium copticola) which was named penicillimide. 324 Alternariol-9-methyl ether 3-O-sulfate 545, previously obtained from Alternaria sp., an endophyte of the Egyptian medicinal plant Polygonum senegalense, 325 was obtained for the rst time from the marine environment from endophytic Alternaria alternata.…”

Antitumor Activity of Quinazolinone Alkaloids Inspired by Marine Natural Products

“…PJX-41 [4], fumiquinazoline F ( 3 ), isolated from the marine-derived fungus Aspergillus fumigatus strain H1-04 and Aspergillus sp. [5,6], and fiscalin B ( 4 ), isolated from the culture of the fugal strain Dichotomomyces cejpii which was recovered from sediments of the Brazilian coast [7]; (ii) compounds with a more complex structure containing several rings such as fumiquinazoline K ( 6 ), isolated from the Mediterranean sponge-derived fungus Aspergillus sp., the soft coral ( Sinularia sp. )-associated fungus Aspergillus fumigatus KMM 4631 [8], and a gorgonian-associated fungus [9]; (iii) spiro compounds such as fumiquinazoline C ( 7 ), isolated from the marine-derived fungus Aspergillus fumigatus strain H1-04, and N -formyllapatin A ( 8 ), isolated from the marine-derived fungus Penicillium adametziodes (AS-53) [10]; (iv) compounds with complex 3-indolyl groups such as cladoquinazoline ( 9 ) and epi-cladoquinazoline ( 10 ), isolated from the mangrove-derived fungus Cladosporium sp.…”

“…For instance, glyantrypine ( 2 ) is an antibacterial agent, active against Vibrio harveyi [16]; fumiquinazolines are antitumor compounds with moderate cytotoxicity [17]; fiscalins are substance P inhibitors and anticancer agents [7,18]; cladoquinazolines ( 9 and 10 ) are active against influenza A virus (H 1 N 1 ); fumiquinazoline S ( 12 ) exhibits a weak inhibition against Na + /K + -ATPase, and N -acetylardeemin ( 14 ) is a potent inhibitor of multidrug resistant (MDR) tumor cells [4,13,19,20]. Moreover, the pyrazino[2,1- b ]quinazoline ring system has been already ascribed as essential for the above-mentioned activities, and its enantioselective effects were observed for their antibacterial activity.…”