ci400132q_si_001.pdf (1.77 MB)
Pharmacophore Assessment Through 3-D QSAR: Evaluation of the Predictive Ability on New Derivatives by the Application on a Series of Antitubercular Agents
journal contribution
posted on 2013-06-24, 00:00 authored by 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 TortorellaPharmacophoric
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.