title: Secondary metabolites from a culture of the fungus Neosartorya pseudofischeri and their in vitro cytostatic activity in human cancer cells.
abstract: Four known (1, 2, 3, and 6) and three new compounds including a 1,4-diacetyl-2,5-dibenzylpiperazine derivative (4), a quinazolinone-containing indole derivative (5), and a new ester of 2,4-dihydroxy-6-methylbenzoic acid (7) were isolated from the fungus Neosartorya pseudofischeri S. W. Peterson. Compound 2 displayed in vitro growth inhibitory activity that ranged between the activities of etoposide and carboplatin, chosen as reference compounds, in six distinct cancer cell lines. Compound 1 displayed less activity than 2. Computer-assisted phase-contrast microscopy-related analysis revealed that 2 displayed cytostatic, not cytotoxic, effects in human U373 glioblastoma and A549 non-small cell lung cancer apoptosis-resistant cells with marked inhibition of mitotic rates. Cancer cells in the remaining phases of the cell cycle were unchanged. Flow cytometry analysis further confirmed that 2 does not induce apoptotic features in U373 or A549 cancer cells. Thus, 2 represents a novel chemical scaffold from which derivatives for anticancer cytostatic compounds can be derived.
authors.affiliation: ICBAS - Instituto de Ciências Biomédicas de Abel Salazar and CIIMAR, Universidade do Porto, Porto, Portugal.
authors.forename: Amnat
authors.initials: A
authors.lastname: Eamvijarn
authors.forename: Anake
authors.initials: A
authors.lastname: Kijjoa
authors.forename: Céline
authors.initials: C
authors.lastname: Bruyère
authors.forename: Véronique
authors.initials: V
authors.lastname: Mathieu
authors.forename: Leka
authors.initials: L
authors.lastname: Manoch
authors.forename: Florence
authors.initials: F
authors.lastname: Lefranc
authors.forename: Artur
authors.initials: A
authors.lastname: Silva
authors.forename: Robert
authors.initials: R
authors.lastname: Kiss
authors.forename: Werner
authors.initials: W
authors.lastname: Herz
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology; D054697:Cytostatic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D004149:Dioxoles / Q000302:isolation & purification / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005909:Glioblastoma / Q000473:pathology; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D009682:Magnetic Resonance Spectroscopy; D008858:Microscopy, Phase-Contrast / Q000379:methods; D008938:Mitosis / Q000187:drug effects; D055326:Neosartorya / Q000737:chemistry* / Q000254:growth & development / Q000302:isolation & purification; D011719:Pyrazines / Q000302:isolation & purification / Q000494:pharmacology; D011725:Pyridines / Q000302:isolation & purification / Q000494:pharmacology; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology; D012988:Soil Microbiology
chemical_list: D000970:Antineoplastic Agents; D054697:Cytostatic Agents; D004149:Dioxoles; D011719:Pyrazines; D011725:Pyridines; D012717:Sesquiterpenes; C472986:brasiliamide B; C082792:pyripyropene A