Anti-AIDS agents 69. Moronic acid and other triterpene derivatives as novel potent anti-HIV agents
Anti-AIDS agents 69. Moronic acid and other triterpene derivatives as novel potent anti-HIV agents
复制标题
DOI：
10.1021/jm0601912
复制
发表时间：
2006-09-07
影响因子：
7.3
通讯作者：
Lee, Kuo-Hsiung
中科院分区：
文献类型：
--
作者：
Yu, Donglei;Sakurai, Yojiro;Lee, Kuo-Hsiung
在一个持续的结构-活性关系的研究，有效的抗HIV药物，七个新的三萜衍生物的设计，合成，并在体外抗病毒活性进行了评价。其中，moronic酸衍生物19、20和21在HIV-1感染的H9淋巴细胞中显示出显著的活性。还针对MT-4细胞系中的HIV-1 NL 4 -3和耐药菌株评价了化合物19和20。化合物19和20显示出比桦木酸类似物8（PA-457）更好的抗病毒特性，桦木酸类似物8已成功完成IIa期临床试验。化合物20显示出有效的抗HIV活性，其对NL 4 -3的EC 50值为0.0085 μ M，对PI-R（一种多重蛋白酶抑制剂抗性菌株）的EC 50值为0.021 μ M，对FHR-2（一种对8具有抗性的HIV菌株）的EC 50值为0.13 μ M。有前途的化合物20已成为一个新的领导修改，并进一步开发20相关化合物作为临床试验的候选人是必要的。
In a continuing structure-activity relationship study of potent anti-HIV agents, seven new triterpene derivatives were designed, synthesized, and evaluated for in vitro antiviral activity. Among them, moronic acid derivatives 19, 20, and 21 showed significant activity in HIV-1 infected H9 lymphocytes. Compounds 19 and 20 were also evaluated against HIV-1 NL4-3 and drug resistant strains in the MT-4 cell line. Compounds 19 and 20 showed better antiviral profiles than the betulinic acid analogue 8 (PA-457), which has successfully completed a Phase IIa clinical trial. Compound 20 showed potent anti-HIV activity with EC50 values of 0.0085 mu M against NL4-3, 0.021 mu M against PI-R (a multiple protease inhibitor resistant strain), and 0.13 mu M against FHR-2 (an HIV strain resistant to 8). Promising compound 20 has become a new lead for modification, and further development of 20-related compounds as clinical trial candidates is warranted.