磷脂酶A2和鞘磷脂合酶双功能抑制剂的设计，合成和活性评价
esign, synthesis, and biological evaluation of novel dual inhibitors of secretory phospholipase A2 and sphingomyelin synthase
分泌型磷脂酶A2和鞘磷脂合酶均为与动脉粥样硬化相关的关键酶。本文设计合成了分别含有吲哚和α-氨基氰结构片断的，以不等长度碳链相连并有不同取代位置的一类新的磷脂酶A2和鞘磷脂合酶双功能抑制剂。体外生物评价结果显示出这些化合物均对两种酶具有抑制活性，其中对鞘磷脂合酶的抑制优于已报道的阳性对照化合物D609。化合物5b和5e分别在肝匀浆和SMS2高表达细胞匀浆上显示出中等的抑制活性，并具有对磷脂酶A2的理想的抑制活性。
he secretory phospholipase A2 (sPLA2) and sphingomyelin (SMS) are the key enzymes to atherosclerosis. A novel series of eight sPLA2 and SMS dual inhibitors containing indole and α-amino cyanide fragments respectively with different length carbon chain and substitution position were designed and synthesized. In vitro biological evaluation showed that all the compounds provided inhibitory effects against both SMS and sPLA2, in which, the SMS inhibitory activities were better than the positive control compound D609. The compounds 5b and 5e had moderate SMS inhibitory effects in liver homogenate and in SMS2 high expression cell homogenate respectively, as well as had ideal sPLA2 inhibitory activities.
门鹏、高星、龚昊隽、周璐、叶德泳
药学生物化学基础医学
动脉粥样硬化分泌性磷脂酶A2鞘磷脂合酶多靶点药物设计双功能抑制剂
atherosclerosissecretory phospholipase A2 (sPLA2)sphingomyelin synthase (SMS)multi-target drug designdual inhibitors
门鹏,高星,龚昊隽,周璐,叶德泳.磷脂酶A2和鞘磷脂合酶双功能抑制剂的设计，合成和活性评价[EB/OL].(2013-02-19)[2025-08-03].http://www.paper.edu.cn/releasepaper/content/201302-315.点此复制
评论