Marinomycins A-D, antitumor-antibiotics of a new structure class from a marine actinomycete of the recently discovered genus "marinispora".
Four antitumor-antibiotics of a new structure class, the marinomycins A-D (1-4), were isolated from the saline culture of a new group of marine actinomycetes, for which we have proposed the name "Marinispora". The structures of the marinomycins, which are unusual macrodiolides composed of dimeric 2-hydroxy-6-alkenyl-benzoic acid lactones with conjugated tetraene-pentahydroxy polyketide chains, were assigned by combined spectral and chemical methods. In room light, marinomycin A slowly isomerizes to its geometrical isomers marinomycins B and C. Marinomycins A-D show significant antimicrobial activities against drug resistant bacterial pathogens and demonstrate impressive and selective cancer cell cytotoxicities against six of the eight melanoma cell lines in the National Cancer Institute's 60 cell line panel. The discovery of these new compounds from a new, chemically rich genus further documents that marine actinomycetes are a significant resource for drug discovery.
Kwon
Hak Cheol
HC
Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California at San Diego, La Jolla, California 92093-0204, USA.
Kauffman
Christopher A
CA
Jensen
Paul R
PR
Fenical
William
W
D039903:Actinobacteria / Q000737:chemistry*; D000475:Alkenes / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D016984:Enterococcus faecium / Q000187:drug effects; D006801:Humans; D007783:Lactones / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D018942:Macrolides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D008545:Melanoma / Q000188:drug therapy; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D013211:Staphylococcus aureus / Q000187:drug effects
D000475:Alkenes; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D007783:Lactones; D018942:Macrolides; C509125:marinomycin A; C509126:marinomycin B; C509121:marinomycin C; C509127:marinomycin D