Extension of the polyanionic cosalane pharmacophore as a strategy for increasing anti-HIV potency.
Extension of the polyanionic cosalane pharmacophore as a strategy for increasing anti-HIV potency.
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聚阴离子 cosalane 药效团的扩展作为增加抗 HIV 效力的策略。
DOI：
10.1021/jm980727m
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发表时间：
1999
影响因子：
7.3
通讯作者：
Rice,WG
中科院分区：
文献类型：
--
作者：
Cushman,M;Insaf,S;Paul,G;Ruell,JA;DeClercq,E;Schols,D;Pannecouque,C;Witvrouw,M;Schaeffer,CA;Turpin,JA;Williamson,K;Rice,WG
抗HIV药物可莎烷抑制gp 120与CD 4的结合以及逆转录前的未定义的附着后事件。几种具有扩展的聚阴离子“药效团”的可莎烷类似物是基于可莎烷与CD 4结合的假设模型设计的。合成的类似物，其中一些显示出抗HIV活性。其中一种新的类似物被发现具有增强的效力，作为一种抗艾滋病毒剂相对于柯沙拉烷本身。虽然新的类似物抑制HIV-1和HIV-2，但它们作为HIV-1的抑制剂比HIV-2更有效。作用机制研究表明，最有效的新类似物抑制病毒包膜与细胞膜的融合，浓度低于其抑制附着的浓度，表明抑制融合是主要的作用机制。
The anti-HIV agent cosalane inhibits both the binding of gp120 to CD4 as well as an undefined postattachment event prior to reverse transcription. Several cosalane analogues having an extended polyanionic “pharmacophore” were designed based on a hypothetical model of the binding of cosalane to CD4. The analogues were synthesized, and a number of them displayed anti-HIV activity. One of the new analogues was found to possess enhanced potency as an anti-HIV agent relative to cosalane itself. Although the new analogues inhibited both HIV-1 and HIV-2, they were more potent as inhibitors of HIV-1 than HIV-2. Mechanism of action studies indicated that the most potent of the new analogues inhibited fusion of the viral envelope with the cell membrane at lower concentrations than it inhibited attachment, suggesting inhibition of fusion as the primary mechanism of action.