title: TLN-05220, TLN-05223, new Echinosporamicin-type antibiotics, and proposed revision of the structure of bravomicins(*).
abstract: The deposited strain of the hazimicin producer, Micromonospora echinospora ssp. challisensis NRRL 12255 has considerable biosynthetic capabilities as revealed by genome scanning. Among these is a locus containing both type I and type II PKS genes. The presumed products of this locus, TLN-05220 (1) and TLN-05223 (2), bear a core backbone composed of six fused rings starting with a 2-pyridone moiety. The structures were confirmed by conventional spectral analyses including MS, and 1D and 2D NMR experiments. Comparison of both the 1H and 13C NMR data of the newly isolated compound with those of echinosporamicin and bravomicin A led us to propose a revision of the structure of the latter to include a 2-pyridone instead of the pyran originally postulated. Both compounds (1 and 2) possessed strong antibacterial activity against a series of gram-positive pathogens including several strains of methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci (VRE), and cytotoxic activities against several human tumor cell lines. The TLN compounds are the first of this group with reported anticancer activity.
authors.affiliation: Institute for Marine Biosciences, National Research Council, Halifax, Nova Scotia, Canada.
authors.forename: Arjun H
authors.initials: AH
authors.lastname: Banskota
authors.forename: Mustapha
authors.initials: M
authors.lastname: Aouidate
authors.forename: Dan
authors.initials: D
authors.lastname: Sørensen
authors.forename: Ashraf
authors.initials: A
authors.lastname: Ibrahim
authors.forename: Mahmood
authors.initials: M
authors.lastname: Piraee
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Zazopoulos
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Alarco
authors.forename: Henriette
authors.initials: H
authors.lastname: Gourdeau
authors.forename: Christophe
authors.initials: C
authors.lastname: Mellon
authors.forename: Chris M
authors.initials: CM
authors.lastname: Farnet
authors.forename: Pierre
authors.initials: P
authors.lastname: Falardeau
authors.forename: James B
authors.initials: JB
authors.lastname: McAlpine
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002277:Carcinoma / Q000188:drug therapy*; D045744:Cell Line, Tumor; D016983:Enterococcus / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D051379:Mice; D008819:Mice, Nude; D008826:Microbial Sensitivity Tests; D008847:Micromonospora / Q000145:classification / Q000254:growth & development / Q000378:metabolism*; D008969:Molecular Sequence Data; D011084:Polycyclic Aromatic Hydrocarbons / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D013329:Structure-Activity Relationship; D020713:Vancomycin Resistance / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D011084:Polycyclic Aromatic Hydrocarbons; C545190:TLN 05220; C545191:TLN 05223