Isolation of dolastatin 10 from the marine cyanobacterium Symploca species VP642 and total stereochemistry and biological evaluation of its analogue symplostatin 1
Isolation of dolastatin 10 from the marine cyanobacterium Symploca species VP642 and total stereochemistry and biological evaluation of its analogue symplostatin 1
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DOI：
10.1021/np010049y
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发表时间：
2001-07-01
影响因子：
5.1
通讯作者：
Corbett, TH
中科院分区：
文献类型：
--
作者：
Luesch, H;Moore, RE;Corbett, TH
有效的抗癌药物多拉他丁10(1)最初是从海兔耳廓多拉贝氏藻中分离出来的，现在我们报道它是从海洋蓝藻Symploca sp.中分离出来的。来自帕劳的VP642。化学上相关的类似物symplostatin 1(2)已从瓜曼和夏威夷品种的海链霉菌中重新分离，并通过确定N，N-二甲基异亮氨酸单元为L来完成其全立体化学。在体内对几种小鼠肿瘤进行了抗肿瘤活性的评价。Symplostatin 1(2)对药物不敏感的乳腺肿瘤和药物不敏感的结肠癌有效，但对两种多药耐药肿瘤仅轻微有效。
The potent antitumor agent dolastatin 10 (1) was originally isolated from the sea hare Dolabella auricularia, and we now report its isolation from the marine cyanobacterium Symploca sp. VP642 from Palau. The chemically related analogue symplostatin 1 (2) has been reisolated from Guamanian and Hawaiian varieties of S. hydnoides and its total stereochemistry completed by determining the N,N-dimethylisoleucine unit to be L. Symplostatin 1 (2), like dolastatin 10 (1), is a potent microtubule inhibitor. The antitumor activity of 2 was assessed in vivo against several murine tumors. Symplostatin 1 (2) was effective against a drug-insensitive mammary tumor and a drug-insensitive colon tumor; however, it was only slightly effective against two MDR tumors.