Dicaffeoyltartaric acid analogues inhibit human immunodeficiency virus type 1 (HIV-1) integrase and HIV-1 replication at nontoxic concentrations.
Dicaffeoyltartaric acid analogues inhibit human immunodeficiency virus type 1 (HIV-1) integrase and HIV-1 replication at nontoxic concentrations.
复制标题
二咖啡酰酒石酸类似物在无毒浓度下可抑制人类免疫缺陷病毒 1 型 (HIV-1) 整合酶和 HIV-1 复制。
DOI：
10.1021/jm010359d
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发表时间：
2002
影响因子：
7.3
通讯作者：
RobinsonJr,WEdward
中科院分区：
文献类型：
--
作者：
Reinke,RyanA;King,PeterJ;Victoria,JosephG;McDougall,BrendaR;Ma,Guoxiang;Mao,Yingqun;Reinecke,ManfredG;RobinsonJr,WEdward
The human immunodeficiency virus type 1 (HIV-1) is a major health problem worldwide. In this study, 17 analogues ofl-chicoric acid, a potent inhibitor of HIV integrase, were studied. Of these analogues, five submicromolar inhibitors of integrase were discovered and 13 compounds with activity against integrase at less than 10 μM were identified. Six demonstrated greater than 10-fold selectivity for HIV replication over cellular toxicity. Ten analogues inhibited HIV replication at nontoxic concentrations. Alteration of the linkages between the two bis-catechol rings, including the use of amides, mixed amide esters, cholate, and alkyl bridges, was explored. Amides were as active as esters but were more toxic in tissue culture. Alkyl and cholate bridges were significantly less potent against HIV-1 integrase in vitro and were inactive against HIV-1 replication. Two amino acid derivates and one digalloylderivative ofl-chicoric acid (l-CA) showed improved selectivity overl-CA against integration in cell culture. These data suggest that in addition to the bis-catechols and free carboxylic acid groups reported previously, polar linkages are important constituents for optimal activity against HIV-1 integrase and that new derivatives can be developed with increased specificity for integration over HIV entry in vivo.
