Synthesis and biological evaluation of synthetic viridins derived from C(20)-heteroalkylation of the steroidal PI-3-kinase inhibitor wortmannin
Synthesis and biological evaluation of synthetic viridins derived from C(20)-heteroalkylation of the steroidal PI-3-kinase inhibitor wortmannin
复制标题
DOI：
10.1039/b405431h
复制
发表时间：
2004-01-01
影响因子：
3.2
通讯作者：
Powis, G
中科院分区：
文献类型：
--
作者：
Wipf, P;Minion, DJ;Powis, G
通过在C（20）处亲核开环从渥曼青霉素制备一系列绿青霉素类似物，并针对信号传导激酶PI-3-激酶和mTOR进行评价。几个亚纳摩尔的酶抑制剂与PI-3-激酶的数量级选择性和对四种癌细胞系的强细胞毒活性进行了鉴定。在十个最有前途的衍生物中，有六个表现出较低的肝毒性和更大的承诺，抑制肿瘤细胞生长比铅结构渥曼青霉素。
A series of viridin analogs was prepared from wortmannin by nucleophilic ring opening at C( 20) and evaluated against the signaling kinases PI-3-kinase and mTOR. Several subnanomolar enzyme inhibitors with orders of magnitude selectivity for PI-3-kinase and strong cytotoxic activity against four cancer cell lines were identified. Among the ten most promising derivatives, six demonstrated lower liver toxicity and greater promise for inhibition of tumor cell growth than the lead structure wortmannin.