Sponge-derived fijianolide polyketide class: Further evaluation of their structural and cytotoxicity properties
Sponge-derived fijianolide polyketide class: Further evaluation of their structural and cytotoxicity properties
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DOI：
10.1021/jm070410z
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发表时间：
2007-08-09
影响因子：
7.3
通讯作者：
Crews, Phillip
中科院分区：
文献类型：
--
作者：
Johnson, Tyler A.;Tenney, Karen;Crews, Phillip
海绵衍生的聚酮大环内酯fijianolides A（1）和B（2），isolaulimalide和laulimalide，具有紫杉醇样微管稳定活性，后者表现出强的细胞毒性。洞察Cacospongia mycofijiensis的地理和表型变异，这将使未来的研究产生的fijianolides的生物合成途径。除了斐济内酯A和B之外，还分离出六种新的斐济内酯D-I（7-12），每种都对大环内酯环的C-20侧链进行了修饰。化合物7-12对HCT- 116和MDA-MB-435细胞系表现出一系列体外活性。斐济内酯8和10显示出破坏间期和有丝分裂，但不如2有效。使用荷瘤严重联合免疫缺陷小鼠对2进行的体内评价表明，在28天内对HCT- 116肿瘤的生长具有显著抑制作用。
The sponge-derived polyketide macrolides fijianolides A (1) and B (2), isolaulimalide and laulimalide, have taxol-like microtubule-stabilizing activity, and the latter exhibits potent cytotoxicity. Insight on the biogeographical and phenotypic variations of Cacospongia mycofijiensis is presented that will enable a future study of the biosynthetic pathway that produces the fijianolides. In addition to fijianolides A and B, six new fijianolides, D-I (7-12), were isolated, each with modifications to the C-20 side chain of the macrolide ring. Compounds 7-12 exhibited a range of in vitro activities against HCT- 116 and MDA-MB-435 cell lines. Fijianolides 8 and 10 were shown to disrupt interphase and mitotic division, but were less potent than 2. An in vivo evaluation of 2 using tumor-bearing severe combined immuno-deficiency mice demonstrated significant inhibition of growth in HCT- 116 tumors over 28 days.