Amantelides A and B, Polyhydroxylated Macrolides with Differential Broad-Spectrum Cytotoxicity from a Guamanian Marine Cyanobacterium.
Amantelides A and B, Polyhydroxylated Macrolides with Differential Broad-Spectrum Cytotoxicity from a Guamanian Marine Cyanobacterium.
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DOI：
10.1021/acs.jnatprod.5b00293
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发表时间：
2015-08-28
影响因子：
5.1
通讯作者：
Luesch H
中科院分区：
文献类型：
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作者：
Salvador-Reyes LA;Sneed J;Paul VJ;Luesch H
细胞毒性指导的分离的关岛蓝藻收集产生新化合物amantelides A（1）和B（2）。这些聚酮化合物的特征在于由1，3-二醇和邻接的1，5-二醇单元和叔丁基取代基组成的40元大环内酯环。Amantelide A（1）对HT 29结肠直肠腺癌和HeLa宫颈癌细胞系显示出有效的细胞毒性，IC 50为亚微摩尔。2中C-33位羟基的乙酰化导致效价降低近10倍。羟基的彻底乙酰化使amantelide A（1）的抗增殖活性降低20-67倍。进一步的生物活性评估表明1具有广谱的生物活性。
Cytotoxicity-guided fractionation of a Guamanian cyanobacterial collection yielded the new compounds amantelides A (1) and B (2). These polyketides are characterized by a 40-membered macrolactone ring consisting of a 1,3-diol and contiguous 1,5-diol units and a tert-butyl substituent. Amantelide A (1) displayed potent cytotoxicity with sub-micromolar IC50 against HT29 colorectal adenocarcinoma and HeLa cervical carcinoma cell lines. Acetylation of the hydroxy group at C-33 in 2 caused a close to 10-fold decrease in potency. Exhaustive acetylation of the hydroxy groups abrogated the antiproliferative activity of amantelide A (1) by 20–67-fold. Further bioactivity assessment of 1 against bacterial pathogens and marine fungi indicated a broad spectrum of bioactivity.