title: Biakamides A-D, Unique Polyketides from a Marine Sponge, Act as Selective Growth Inhibitors of Tumor Cells Adapted to Nutrient Starvation.
abstract: Biakamides A-D, novel unusually unique polyketides, were isolated from an Indonesian marine sponge (Petrosaspongia sp.) with a constructed bioassay using PANC-1 human pancreatic cancer cells. Through detailed analyses of the one- and two-dimensional NMR spectra of biakamides, planar chemical structures possessing a terminal thiazole, two N-methyl amides, a chloromethylene, and a substituted butyryl moiety were obtained. After elucidation of the configuration of the secondary alcohol moiety in biakamides A and B, the absolute stereostructures of the two secondary methyl groups in biakamides A-D were determined by the asymmetric total syntheses of all possible stereoisomers from the optically pure monoprotected 2,4-dimethyl-1,5-diol. Biakamides A-D showed selective antiproliferative activities against PANC-1 cells cultured under glucose-deficient conditions in a concentration-dependent manner. The primary mode of action of biakamides was found to be inhibition of complex I in the mitochondrial electron transport chain.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University , Yamada-oka 1-6, Suita, Osaka 565-0871, Japan.
authors.forename: Naoyuki
authors.identifier: 0000-0001-7639-5553
authors.initials: N
authors.lastname: Kotoku
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University , Yamada-oka 1-6, Suita, Osaka 565-0871, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Ishida
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University , Yamada-oka 1-6, Suita, Osaka 565-0871, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Matsumoto
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University , Yamada-oka 1-6, Suita, Osaka 565-0871, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Arai
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University , Yamada-oka 1-6, Suita, Osaka 565-0871, Japan.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Toda
authors.affiliation: Department of Chemistry, Faculty of Science, Lampung University , Jl. Prof. Dr. Sumantri Brodjonegoro No. 1, Bandar, Lampung 35145, Indonesia.
authors.forename: Andi
authors.initials: A
authors.lastname: Setiawan
authors.affiliation: School of Pharmacy, Kindai University , 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Muraoka
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University , Yamada-oka 1-6, Suita, Osaka 565-0871, Japan.
authors.forename: Motomasa
authors.initials: M
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008968:Molecular Conformation; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D061065:Polyketides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011161:Porifera / Q000737:chemistry*; D013217:Starvation / Q000188:drug therapy* / Q000473:pathology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D061065:Polyketides