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Quantifying Agonist Activity at G Protein-coupled Receptors
Published on: December 26, 2011
A genetic-function-approximation-based QSAR model for the affinity of arylpiperazines toward alpha1 adrenoceptors
Laura Maccari1, Matteo Magnani, Giovannella Strappaghetti
1Dipartimento Farmaco Chimico Tecnologico, Università degli Studi di Siena, Via Alcide de Gasperi, 2, I-53100 Siena, Italy.
Abstract:
The genetic function approximation (GFA) algorithm has been used to derive a three-term QSAR equation able to correlate the structural properties of arylpiperazine derivatives with their affinity toward the alpha1 adrenoceptor (alpha1-AR). The number of rotatable bonds, the hydrogen-bond properties, and a variable belonging to a topological family of descriptors (chi) showed significant roles in the binding process toward alpha1-AR. The new model was also compared to a previous pharmacophore for alpha1-AR antagonists and a QSAR model for alpha2-AR antagonists with the aim of finding common or different key determinants influencing both affinity and selectivity toward alpha1- and alpha2-AR.
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