针对新型HIV-1整合酶抑制剂的高效三维数据库筛选

Efficient 3D database screening for novel HIV-1 IN inhibitors.

作者信息

Barreca Maria Letizia, Rao Angela, De Luca Laura, Zappalà Maria, Gurnari Cristina, Monforte Pietro, De Clercq Erik, Van Maele Bénédicte, Debyser Zeger, Witvrouw Myriam, Briggs James M, Chimirri Alba

机构信息

Dipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, 98168 Messina, Italy.

出版信息

J Chem Inf Comput Sci. 2004 Jul-Aug;44(4):1450-5. doi: 10.1021/ci034296e.

DOI:10.1021/ci034296e

PMID:15272853

Abstract

We describe the use of pharmacophore modeling as an efficient tool in the discovery of novel HIV-1 integrase (IN) inhibitors. A three-dimensional hypothetical model for the binding of diketo acid analogues to the enzyme was built by means of the Catalyst program. Using these models as a query for virtual screening, we found several compounds that contain the specified 3D patterns of chemical functions. Biological testing shows that our strategy was successful in searching for new structural leads as HIV-1 IN inhibitors.

摘要

我们描述了将药效团建模作为发现新型HIV-1整合酶（IN）抑制剂的有效工具。借助Catalyst程序构建了二酮酸类似物与该酶结合的三维假设模型。使用这些模型作为虚拟筛选的查询，我们发现了几种含有特定化学功能三维模式的化合物。生物学测试表明，我们的策略成功地找到了作为HIV-1 IN抑制剂的新结构先导物。