title: 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.).
authors.affiliation: Departamento de Química Orgânica e Inorgânica, Universidade Federal do Ceará, Campus do Pici, P.O. Box 6044, 60.455-970, Fortaleza-CE, Brazil (phone: +55-85-33669144).
authors.forename: Bárbara S F
authors.initials: BS
authors.lastname: Rodrigues
authors.forename: Bianca D B
authors.initials: BD
authors.lastname: Sahm
authors.forename: Paula C
authors.initials: PC
authors.lastname: Jimenez
authors.forename: Francisco C L
authors.initials: FC
authors.lastname: Pinto
authors.forename: Jair
authors.initials: J
authors.lastname: Mafezoli
authors.forename: Marcos C
authors.initials: MC
authors.lastname: Mattos
authors.forename: Edson
authors.initials: E
authors.lastname: Rodrigues-Filho
authors.forename: Ludwig H
authors.initials: LH
authors.lastname: Pfenning
authors.forename: Lucas M
authors.initials: LM
authors.lastname: Abreu
authors.forename: Letícia V
authors.initials: LV
authors.lastname: Costa-Lotufo
authors.forename: Maria C F
authors.initials: MC
authors.lastname: Oliveira
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D001688:Biological Products / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D001938:Brazil; D003110:Colonic Neoplasms / Q000188:drug therapy; D005658:Fungi / Q000737:chemistry* / Q000235:genetics; D019015:Geologic Sediments / Q000382:microbiology*; D005912:Gliotoxin / Q000031:analogs & derivatives / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D045325:HCT116 Cells; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D010802:Phylogeny; D011799:Quinazolines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D007211:Indoles; D011799:Quinazolines; C081408:fiscalin B; D005912:Gliotoxin
keywords: Cytotoxic activity; Dichotomomyces cejpii; Fiscalin B; Fungi; Gliotoxin; Gliotoxin G, acetyl-