title: Kalkipyrone B, a marine cyanobacterial γ-pyrone possessing cytotoxic and anti-fungal activities.
abstract: Bioassay-guided fractionation of two marine cyanobacterial extracts using the H-460 human lung cancer cell line and the OVC-5 human ovarian cancer cell line led to the isolation of three related α-methoxy-β, β'-dimethyl-γ-pyrones each containing a modified alkyl chain, one of which was identified as the previously reported kalkipyrone and designated kalkipyrone A. The second compound was an analog designated kalkipyrone B. The third was identified as the recently reported yoshinone A, also isolated from a marine cyanobacterium. Kalkipyrone A and B were obtained from a field-collection of the cyanobacterium Leptolyngbya sp. from Fagasa Bay, American Samoa, while yoshinone A was isolated from a field-collection of cyanobacteria (cf. Schizothrix sp.) from Panama. One-dimensional and two-dimensional NMR experiments were used to determine the overall structures and relative configurations of the kalkipyrones, and the absolute configuration of kalkipyrone B was determined by (1)H NMR analysis of diastereomeric Mosher's esters. Kalkipyrone A showed good cytotoxicity to H-460 human lung cancer cells (EC50=0.9μM), while kalkipyrone B and yoshinone A were less active (EC50=9.0μM and >10μM, respectively). Both kalkipyrone A and B showed moderate toxicity to Saccharomyces cerevisiae ABC16-Monster strain (IC50=14.6 and 13.4μM, respectively), whereas yoshinone A was of low toxicity to this yeast strain (IC50=63.8μM).
authors.affiliation: Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, 8615 Kennel Way, La Jolla, CA 92037, United States.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Bertin
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmacy, Trakya University, Edirne 22030, Turkey.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Demirkiran
authors.affiliation: Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, 8615 Kennel Way, La Jolla, CA 92037, United States.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Navarro
authors.affiliation: Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, 8615 Kennel Way, La Jolla, CA 92037, United States.
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Moss
authors.affiliation: Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, 8615 Kennel Way, La Jolla, CA 92037, United States; Chemistry & Biochemistry Program, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, United States.
authors.forename: John
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, University of California, San Diego, School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093, United States.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Goldgof
authors.affiliation: Department of Pediatrics, University of California, San Diego, School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093, United States.
authors.forename: Edgar
authors.initials: E
authors.lastname: Vigil
authors.affiliation: Department of Pediatrics, University of California, San Diego, School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093, United States.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Winzeler
authors.affiliation: Henry Ford Health System, Department of Internal Medicine, Josephine Ford Cancer Center, 440 Burroughs, Room 415, Detroit, MI 48202, United States.
authors.forename: Fred A
authors.initials: FA
authors.lastname: Valeriote
authors.affiliation: Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, 8615 Kennel Way, La Jolla, CA 92037, United States; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, United States. Electronic address: wgerwick@ucsd.edu.
authors.forename: William H
authors.initials: WH
authors.lastname: Gerwick
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000458:Cyanobacteria / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008386:Marine Biology; D015394:Molecular Structure; D010176:Panama; D011753:Pyrones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D011753:Pyrones; C000610827:kalkipyrone A; C000610826:kalkipyrone B
keywords: Cyanobacteria; Kalkipyrone; Leptolyngbya; Moorea; Polyketide; Schizothrix; Yoshinone