The role of electronic and conformational properties in the activity of 5-HT3 receptor antagonists
| Autor: | C.A. Rizzi, Giovanni Battista Schiavi, Giorgio Moro, Ugo Cosentino, Ettore Giraldo, Myrna Gil Quintero, Marco Turconi |
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| Rok vydání: | 1993 |
| Předmět: |
education.field_of_study
Quantitative structure–activity relationship biology Correlation coefficient Stereochemistry Chemistry Population Biological activity Condensed Matter Physics Biochemistry 5-HT3 receptor Partial least squares regression biology.protein Molecule Physical and Theoretical Chemistry Pharmacophore education |
| Zdroj: | Journal of Molecular Structure: THEOCHEM. 286:275-291 |
| ISSN: | 0166-1280 |
| Popis: | The conformational and electronic properties of 11 5-HT 3 receptor antagonists, were investigated to rationalize their biological activity. All compounds fulfill the previously reported geometrical requirements for the pharmacophore, although they show a wide spectrum of activities. Quantitative structure-activity relationships (QSAR) models were searched using the cross-validated partial least squares technique. The results of the QSAR analysis show that a unique model can rationalize both the in vitro (affinity, K d ) and the in vivo (50% inhibitory dose, ID 50 ) activities. This model includes the value of the molecular electrostatic potential minimum above the aromatic fragment, used as an index of the π-electron density, as well as the relative population of the anti-periplanar (app, the “active”) conformation. Two other models were also obtained that include electrophilic superdelocalizability indexes. Although these models give a more satisfactory value of the cross-validated correlation coefficient ( R 2 cv ), they represent two different models for K d and ID 50 which is in contrast with the experimental evidence that a correlation exists between these two activities. It is concluded that the use of electronic and conformational properties in addition to the geometrical characteristics may better describe and predict the activity of 5-HT 3 receptor antagonists, than the use of geometrical characteristics alone. |
| Databáze: | OpenAIRE |
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