Journal
JOURNAL OF ORGANIC CHEMISTRY
Volume 82, Issue 3, Pages 1705-1718Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.joc.6b02948
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Funding
- MEXT/JSPS KAKENHI [JP23102005, JP26242074, JP15K07996]
- Platform Project for Supporting Drug Discovery and Life Science Research (Platform for Drug Discovery, Informatics, and Structural Life Science) from MEXT
- Japan Agency for Medical Research and Development (AMED)
- Grants-in-Aid for Scientific Research [15K07996, 26305002, 16K08313, 15H03114, 26242074] Funding Source: KAKEN
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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.
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