ANTIMALARIAL ACTIVITY OF NEW WATER-SOLUBLE DIHYDROARTEMISININ DERIVATIVES .2. STEREOSPECIFICITY OF THE ETHER SIDE-CHAIN
ANTIMALARIAL ACTIVITY OF NEW WATER-SOLUBLE DIHYDROARTEMISININ DERIVATIVES .2. STEREOSPECIFICITY OF THE ETHER SIDE-CHAIN
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DOI：
10.1021/jm00126a017
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发表时间：
1989-06-01
影响因子：
7.3
通讯作者：
KLAYMAN, DL
中科院分区：
文献类型：
--
作者：
LIN, AJ;LEE, M;KLAYMAN, DL
制备了一系列具有光学活性侧链的新型水解陈旧水溶性双氢青蒿素衍生物，作为潜在的抗疟药物。这是为了制备活性优于蒿酸的化合物，并检查引入的烷基侧链的立体特异性对生物特性的影响。酯衍生物(6a-d)对两种恶性疟原虫菌株(D-6和W-2)具有优于青蒿素、蒿甲醚和蒿乙醚的体外活性；然而，酯转化为其相应的酸会大大降低其抗疟活性。没有一种新酸具有优于蒿酸的体外抗疟活性。尽管所测试的酸（7a-d）的抗疟活性立体特异性似乎有限，但酯之间的抗疟活性存在显着差异。
A new series of hydrolytically stale and water-soluble dihydroartemisinin derivatives with optically active side chains was prepared as potential antimalarial agents. This was an effort to prepare compounds with activity superior to that of artelinic acid and to examine the impact of the stereospecificity of the introduced alkyl side chain on biological properties. The ester derivatives (6a-d) possess superior in vitro activity to artemisinin, artemether, and arteether against two strains of Plasmodium falciparum (D-6 and W-2); however, conversion of the esters to their corresponding acids drastically reduces their antimalarial activity. None of the new acids possess in vitro antimalarial activity superior to that of artelinic acid. Although there appears to be limited stereospecificity for antimalarial activity among the acids (7a-d) tested, significant differences in antimalarial activity was seen among the esters.