title: Isolation and characterization of unusual hydrazides from Streptomyces sp. impact of the cultivation support and extraction procedure.
abstract: Three novel hydrazides, geralcins C-E (1-3), were isolated from Streptomyces sp. LMA-545, together with MH-031 and geralcins A and B. This unusual family of compounds was isolated from liquid-state and agar-supported fermentation using Amberlite XAD-16 solid-phase extraction during the cultivation step. The use of such neutral resin during the cultivation step allowed the specific adsorption of microbial secondary metabolites, avoiding any contamination of the crude extracts by the constituents of the culture medium. The trapped compounds were eluted from the resin with methanol, and their structures elucidated using (1)H, (13)C, and (15)N NMR spectroscopic analysis and high-resolution mass spectrometry. Molecular modeling calculations were applied in order to support structural attributions. No antimicrobial, cytotoxic, or DnaG-inhibition activities were detected for geralcins D and E. Geralcin C has no antimicrobial activity but exhibited an IC(50) of 0.8 μM against KB and HCT116 cancer cell lines. Furthermore, geralcin C inhibited the E. coli DnaG primase, a Gram-negative antimicrobial target, with an IC(50) of 0.7 mM.
authors: Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles ICSN, Centre National de la Recherche Scientifique CNRS, Avenue de la Terrasse, Gif-sur-Yvette, France.
authors: Géraldine
authors: G
authors: Le Goff
authors: Marie-Thérèse
authors: MT
authors: Martin
authors: Bogdan I
authors: BI
authors: Iorga
authors: Emilie
authors: E
authors: Adelin
authors: Claudine
authors: C
authors: Servy
authors: Sylvie
authors: S
authors: Cortial
authors: Jamal
authors: J
authors: Ouazzani
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives; D019915:DNA Primase / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004926:Escherichia coli / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D006834:Hydrazines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D007624:KB Cells; D008826:Microbial Sensitivity Tests; D019906:Nuclear Magnetic Resonance, Biomolecular; D013302:Streptomyces / Q000737:chemistry*
chemical_list: D006834:Hydrazines; C580648:geralcin C; C071013:3-(2-oxo-2,5-dihydro-3-furanyl)propanoic acid; D019915:DNA Primase; D015107:4-Butyrolactone