title: HLE-inhibitory alkaloids with a polyketide skeleton from the marine-derived fungus Coniothyrium cereale.
abstract: The marine endophytic fungus Coniothyrium cereale produces the structurally unusual polyketide-type alkaloids (-)-cereolactam (1) and (-)-cereoaldomine (3), incorporating a lactam and an imine functionality, respectively, as well as the related metabolite (-)-trypethelone (2). Compounds 1 and 3 showed selective inhibition of human leukocyte elastase with IC50 values of 9.28 and 3.01 μM, respectively. Compound 2 was found to be inhibitory toward Mycobacterium phlei, Staphylococcus aureus, and Escherichia coli and also cytotoxic against mouse fibroblast cells (IC50=7.5 μM).
authors.affiliation: Institute for Pharmaceutical Biology, University of Bonn, 53115 Bonn, Germany.
authors.forename: Mahmoud Fahmi
authors.initials: MF
authors.lastname: Elsebai
authors.forename: Lavanya
authors.initials: L
authors.lastname: Natesan
authors.forename: Stefan
authors.initials: S
authors.lastname: Kehraus
authors.forename: Ietidal E
authors.initials: IE
authors.lastname: Mohamed
authors.forename: Gregor
authors.initials: G
authors.lastname: Schnakenburg
authors.forename: Florenz
authors.initials: F
authors.lastname: Sasse
authors.forename: Saad
authors.initials: S
authors.lastname: Shaaban
authors.forename: Michael
authors.initials: M
authors.lastname: Gütschow
authors.forename: Gabriele M
authors.initials: GM
authors.lastname: König
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000818:Animals; D001203:Ascomycota / Q000737:chemistry*; D004926:Escherichia coli / Q000187:drug effects; D005347:Fibroblasts; D006801:Humans; D020128:Inhibitory Concentration 50; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors*; D008386:Marine Biology; D051379:Mice; D015394:Molecular Structure; D009168:Mycobacterium phlei / Q000187:drug effects; D061065:Polyketides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects; D013237:Stereoisomerism
chemical_list: D000470:Alkaloids; D061065:Polyketides; C569091:cereolactam; D019272:Leukocyte Elastase