通过分子拓扑学筛选出的抗鸟分枝杆菌复合群的新型药物：一种虚拟筛选方法。
New agents active against Mycobacterium avium complex selected by molecular topology: a virtual screening method.
作者信息
García-García Angeles, Gálvez Jorge, de Julián-Ortiz Jesus-Vicente, García-Domenech Ramón, Muñoz Carlos, Guna Remedios, Borrás Rafael
机构信息
Unidad de Investigación de Diseño de Fármacos y Conectividad Molecular, Departamento de Química Física, Facultad de Farmacia, Universitat de València, 46100 Burjassot, Valencia.
出版信息
J Antimicrob Chemother. 2004 Jan;53(1):65-73. doi: 10.1093/jac/dkh014. Epub 2003 Nov 25.
OBJECTIVES
In order to select new drugs and to predict their in vitro activity against Mycobacterium avium complex (MAC), new quantitative structure-activity relationship (QSAR) models were developed.
METHODS
The activities against MAC of 29 structurally heterogeneous drugs were examined by means of linear discriminant analysis (LDA) and multilinear regression analysis (MLRA) by using topological indices (TI) as structural descriptors. In vitro antimycobacterial activities were determined by a broth microdilution method with 7H9 medium.
RESULTS
The topological model obtained successfully classifies over 80% of compounds as active or inactive; consequently, it was applied in the search for new molecules active against MAC. From among the selected candidates demonstrating in vitro activity, aflatoxin B1, benzalkonium chloride and pentamidine stand out, with MIC50s between 4 and 32 mg/L.
CONCLUSION
The method described in this work is able to select molecules active against MAC.
目的
为了筛选新药并预测其对鸟分枝杆菌复合群（MAC）的体外活性，开发了新的定量构效关系（QSAR）模型。
方法
以拓扑指数（TI）作为结构描述符，通过线性判别分析（LDA）和多元线性回归分析（MLRA）研究了29种结构各异的药物对MAC的活性。采用含7H9培养基的肉汤微量稀释法测定体外抗分枝杆菌活性。
结果
所获得的拓扑模型成功地将80%以上的化合物分类为有活性或无活性；因此，它被用于寻找对MAC有活性的新分子。在显示出体外活性的选定候选物中，黄曲霉毒素B1、苯扎氯铵和喷他脒表现突出，MIC50在4至32mg/L之间。
结论
本研究中描述的方法能够筛选出对MAC有活性的分子。
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