Conjugates of betulin derivatives with AZT as potent anti-HIV agents
Conjugates of betulin derivatives with AZT as potent anti-HIV agents
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DOI：
10.1016/j.bmc.2010.06.092
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发表时间：
2010-09-01
影响因子：
3.5
通讯作者：
Takaishi, Yoshihisa
中科院分区：
文献类型：
--
作者：
Xiong, Juan;Kashiwada, Yoshiki;Takaishi, Yoshihisa
基于我们以前报道的有效的抗HIV三萜先导化合物，包括3-O-酰基和3，28-二-O-酰基桦木醇，制备了14种新的抗HIV药物3，28-二-O-酰基桦木醇与AZT的缀合物。9个偶联物（49-53、55、56、59和60）在亚微摩尔水平显示出有效的抗HIV活性，在HIV-1（NL 4 -3）感染的MT-4细胞中EC（50）值范围为0.040 - 0.098 μ M。这些化合物与3-O-（3 '，3'-二甲基琥珀酰基）桦木酸（2）等效或更有效，目前该化合物正处于IIb期抗艾滋病临床试验中。(C)2010爱思唯尔有限公司保留所有权利。
Fourteen novel conjugates of 3,28-di-O-acylbetulins with AZT were prepared as anti-HIV agents, based on our previously reported potent anti-HIV triterpene leads, including 3-O-acyl and 3,28-di-O-acylbetulins. Nine of the conjugates (49-53, 55, 56, 59, and 60) exhibited potent anti-HIV activity at the submicromolar level, with EC(50) values ranging from 0.040 to 0.098 mu M in HIV-1(NL4-3) infected MT-4 cells. These compounds were equipotent or more potent than 3-O-(3',3'-dimethylsuccinyl) betulinic acid (2), which is currently in Phase IIb anti-AIDS clinical trial. (C) 2010 Elsevier Ltd. All rights reserved.