Bertin Matthew J, Demirkiran Ozlem, Navarro Gabriel, Moss Nathan A, Lee John, Goldgof Gregory M, Vigil Edgar, Winzeler Elizabeth A, Valeriote Fred A, Gerwick William H
Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, 8615 Kennel Way, La Jolla, CA 92037, United States.
Department of Pharmacognosy, Faculty of Pharmacy, Trakya University, Edirne 22030, Turkey.
Phytochemistry. 2016 Feb;122:113-118. doi: 10.1016/j.phytochem.2015.11.011. Epub 2015 Nov 26.
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).
利用H - 460人肺癌细胞系和OVC - 5人卵巢癌细胞系对两种海洋蓝藻提取物进行生物测定导向的分级分离，得到了三种相关的α - 甲氧基 - β,β'- 二甲基 - γ - 吡喃酮，每种都含有一条修饰的烷基链，其中一种被鉴定为先前报道的kalkipyrone，并命名为kalkipyrone A。第二种化合物是一种类似物，命名为kalkipyrone B。第三种被鉴定为最近报道的yoshinone A，它也从一种海洋蓝藻中分离得到。Kalkipyrone A和B是从美属萨摩亚法加萨湾采集的蓝藻Leptolyngbya sp.中获得的，而yoshinone A是从巴拿马采集的蓝藻（参照Schizothrix sp.）中分离得到的。通过一维和二维核磁共振实验确定了kalkipyrones的整体结构和相对构型，kalkipyrone B的绝对构型通过非对映体莫舍尔酯的(1)H NMR分析确定。Kalkipyrone A对H - 460人肺癌细胞显示出良好的细胞毒性（EC50 = 0.9μM），而kalkipyrone B和yoshinone A活性较低（分别为EC50 = 9.0μM和>10μM）。Kalkipyrone A和B对酿酒酵母ABC16 - Monster菌株均显示出中等毒性（IC50分别为14.6和13.4μM），而yoshinone A对该酵母菌株毒性较低（IC50 = 63.8μM）。
