Pharmacophore Assessment Through 3-D QSAR: Evaluation of the Predictive Ability on New Derivatives by the Application on a Series of Antitubercular Agents
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- 作者：Laura Friggeri ; Flavio Ballante ; Rino Ragno ; Ira Musmuca ; Daniela De Vita ; Fabrizio Manetti ; Mariangela Biava ; Luigi Scipione ; Roberto Di Santo ; Roberta Costi ; Marta Feroci ; Silvano Tortorella
- 刊名：Journal of Chemical Information and Modeling
- 出版年：2013
- 出版时间：June 24, 2013
- 年：2013
- 卷：53
- 期：6
- 页码：1463-1474
- 全文大小：652K
- 年卷期：v.53,no.6(June 24, 2013)
- ISSN：1549-960X
文摘
Pharmacophoric mapping is a useful procedure to frame, especially when crystallographic receptor structures are unavailable as in ligand-based studies, the hypothetical site of interaction. In this study, 71 pyrrole derivatives active against M. tuberculosis were used to derive through a recent new 3-D QSAR protocol, 3-D QSAutogrid/R, several predictive 3-D QSAR models on compounds aligned by a previously reported pharmacophoric application. A final multiprobe (MP) 3-D QSAR model was then obtained configuring itself as a tool to derive pharmacophoric quantitative models. To stress the applicability of the described models, an external test set of unrelated and newly synthesized series of R-4-amino-3-isoxazolidinone derivatives found to be active at micromolar level against M. tuberculosis was used, and the predicted bioactivities were in good agreement with the experimental values. The 3-D QSAutogrid/R procedure proved to be able to correlate by a single multi-informative scenario the different activity molecular profiles thus confirming its usefulness in the rational drug design approach.