title: Piperazimycins: cytotoxic hexadepsipeptides from a marine-derived bacterium of the genus Streptomyces.
abstract: Three potent cancer cell cytotoxins, piperazimycins A-C (1-3), have been isolated from the fermentation broth of a Streptomyces sp., cultivated from marine sediments near the island of Guam. The structures of these cyclic hexadepsipeptides were assigned by a combination of spectral, chemical, and crystallographic methods. The piperazimycins are composed of rare amino acids, including hydroxyacetic acid, alpha-methylserine, gamma-hydroxypiperazic acid, and gamma-chloropiperazic acid. The novel amino acid residues 2-amino-8-methyl-4,6-nonadienoic acid and 2-amino-8-methyl-4,6-decadienoic acid were found as components of piperazimycins A and C, respectively. When screened in the National Cancer Institute's 60 cancer cell line panel, piperazimycin A exhibited potent in vitro cytotoxicity toward multiple tumor cell lines with a mean GI50 of 100 nM.
authors.affiliation: Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California-San Diego, La Jolla, California 92093-0204, USA.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Miller
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Kauffman
authors.forename: Paul R
authors.initials: PR
authors.lastname: Jensen
authors.forename: William
authors.initials: W
authors.lastname: Fenical
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D047630:Depsipeptides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods / Q000592:standards; D008958:Models, Molecular; D008968:Molecular Conformation; D012015:Reference Standards; D012680:Sensitivity and Specificity; D013237:Stereoisomerism; D013302:Streptomyces / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D047630:Depsipeptides; C518107:piperazimycin A; C518109:piperazimycin B; C518108:piperazimycin C