Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Juiz de Fora, Juiz de Fora, MG, Brazil.
Curr Med Chem. 2013;20(5):724-33. doi: 10.2174/092986713804999349.
Twenty analogues of the anti-HIV-1 integrase (IN) inhibitors dicaffeoylquinic acids (DCQAs) were prepared. Their IC(50) values for 3'-end processing and strand transfer against recombinant HIV-1IN were determined in vitro, and their cell toxicities and EC(50) against HIV-1 were measured in cells (ex vivo). Acetylated or benzylated and/or with cyclohexylidene group compounds exhibited no inhibition of integration in biochemical assays or viral replication in HIV-infected cells, with the exception of 16 and 36. Removal of these groups, however, correlated with potent inhibition. Compounds 19, 31, and 38, all digalloyls, exhibited the most robust inhibitory performance in biochemical assays as well as in cell culture and less toxicity than other molecules in the current study.
合成了 20 种抗 HIV-1 整合酶（IN）抑制剂二咖啡酰奎宁酸（DCQAs）类似物。在体外测定了它们对重组 HIV-1IN 的 3'-末端加工和链转移的 IC50 值，并在细胞（离体）中测定了它们对 HIV-1 的细胞毒性和 EC50 值。乙酰化或苄基化和/或环己亚基化合物在生化测定或 HIV 感染细胞中的病毒复制中没有表现出整合抑制作用，除了 16 和 36。然而，去除这些基团与有效的抑制作用相关。所有都是双咖啡酰基的化合物 19、31 和 38，在生化测定以及细胞培养中表现出最强大的抑制作用，并且比本研究中的其他分子毒性更小。
