3D-QSAR Approaches in Drug Design: Perspectives to Generate Reliable CoMFA Models
Cleber Camilo Melo-Filho,
Rodolpho Campos Braga,
Carolina Horta Andrade.
Drug discovery is mostly guided by innovative and knowledge by the application of experimental and
computational approaches. Quantitative structure-activity relationships (QSAR) have a critical task in the discovery and
optimization of lead compounds, thereby contributing to the development of new chemical entities. 3D-QSAR methods
use the information of the tridimensional molecular structure of ligands and can be applied to elucidate the relationships
between 3D molecular interactions and their measured biological property, therefore, providing a rational approach for the
development of new potential compounds. The purpose of this review is to provide a perspective of the utility of 3DQSAR
approaches in drug design, focusing on progress, challenges and future orientations. The essential steps involved to
generate reliable and predictive CoMFA models are discussed. Moreover, we present an example of application of a
CoMFA study to derive 3D-QSAR models for a series of oxadiazoles inhibitors of Schistosoma mansoni Thioredoxin
Glutathione Reductase (SmTGR).
Keywords: 3D-QSAR, alignment, CoMFA, docking, drug design, pharmacophore.
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