抗艾滋病药物88. 通过点击化学制备的桦木醇和桦木酸与齐多夫定的抗HIV缀合物。
Anti-AIDS agents 88. Anti-HIV conjugates of betulin and betulinic acid with AZT prepared via click chemistry.
作者信息
Bori Ibrahim D, Hung Hsin-Yi, Qian Keduo, Chen Chin-Ho, Morris-Natschke Susan L, Lee Kuo-Hsiung
机构信息
Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.
出版信息
Tetrahedron Lett. 2012 Apr 11;53(15):1987-1989. doi: 10.1016/j.tetlet.2012.02.022.
Abstract
In the present study, a new strategy to link AZT with betulin/betulinic acid (BA) by click chemistry was designed and achieved. This conjugation via a triazole linkage offers a new direction for modification of anti-HIV triterpenes. Click chemistry provides an easy and productive way for linking two molecules, even when one of them is a large natural product. Among the newly synthesized conjugates, compounds 15 and 16 showed potent anti-HIV activity with EC(50) values of 0.067 and 0.10 µM, respectively, which are comparable to that of AZT (EC(50): 0.10 µM) in the same assay.
摘要
在本研究中，设计并实现了一种通过点击化学将齐多夫定（AZT）与桦木醇/桦木酸（BA）连接的新策略。通过三唑键的这种共轭为抗HIV三萜类化合物的修饰提供了新方向。点击化学为连接两个分子提供了一种简便且高效的方法，即使其中一个是大型天然产物。在新合成的共轭物中，化合物15和16表现出强效抗HIV活性，其半数有效浓度（EC(50)）值分别为0.067和0.10 μM，在相同测定中与AZT（EC(50)：0.10 μM）相当。
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