Pharmacophore assessment through 3-D QSAR: evaluation of the predictive ability on new derivatives by the application on a series of antitubercular agents.
2Rome Center for Molecular Design (Rome Center for Molecular Design, Dipartimento di Chimica e Tecnologie del Farmaco, Università degli Studi di Roma "La Sapienza", P. le A. Moro 5, 00185 Roma - Italy)
Abstract : 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.
Laura Friggeri, Flavio Ballante, Rino Ragno, Ira Musmuca, Daniela de Vita, et al.. Pharmacophore assessment through 3-D QSAR: evaluation of the predictive ability on new derivatives by the application on a series of antitubercular agents.. Journal of Chemical Information and Modeling, American Chemical Society, 2013, 53 (6), pp.1463-74. ⟨10.1021/ci400132q⟩. ⟨pasteur-00968810⟩