A Theoretical Study of the Relationships between Electronic Structure and Inhibitory Effects of Caffeine Derivatives on Neoplastic Transformation
Gaston Assongba Kpotin *
Laboratory of Theoretical Chemistry and Molecular Spectroscopy (LACTHESMO), Faculty of Sciences and Technologies, University of Abomey-Calavi, 01BP1326 Cotonou, Benin
Gauthier Kankinou
Laboratory of Theoretical Chemistry and Molecular Spectroscopy (LACTHESMO), Faculty of Sciences and Technologies, University of Abomey-Calavi, 01BP1326 Cotonou, Benin
Urbain A. Kuevi
Laboratory of Theoretical Chemistry and Molecular Spectroscopy (LACTHESMO), Faculty of Sciences and Technologies, University of Abomey-Calavi, 01BP1326 Cotonou, Benin
Juan S. Gómez-Jeria
Quantum Pharmacology Unit, Department of Chemistry, Faculty of Sciences, University of Chile, Las Palmeras 3425, Santiago 7800003, Chile
Jean-Baptiste Mensah
Laboratory of Theoretical Chemistry and Molecular Spectroscopy (LACTHESMO), Faculty of Sciences and Technologies, University of Abomey-Calavi, 01BP1326 Cotonou, Benin
*Author to whom correspondence should be addressed.
Abstract
A DFT study of the relationships between electronic structure and inhibitory effects of caffeine derivatives on neoplastic transformation was carried out. We obtain one statistically significant equation (R=0.97, R²= 0.94, adjusted R²= 0.92, F(7,34) =71.40 (p<0.00001), SD=0.14), relating the variation of the biological activity with the variation of the values of a definite set of local atomic reactivity indices. Based on the analysis of the results, a partial pharmacophore was built that can be employed as a tool for the development of more active molecules. Calculations have been performed by DFT/B3LYP method in the 6-31G orbital basis set.
Keywords: Caffeine, anticancer, QSAR, pharmacophore, DFT, electronic structure