QUANTUM CHEMICAL STUDY OF THE RELATIONSHIPS BETWEEN ELECTRONIC STRUCTURE AND PHARMACOKINETIC PROFILE, INHIBITORY STRENGTH TOWARD HEPATITIS C VIRUS NS5B POLYMERASE AND HCV REPLICONS OF INDOLE-BASED COMPOUNDS

Journal of The Chilean Chemical Society

ALARCÓN, DIEGO A¹  DE LA VEGA, AMAYA PAZ¹  GÓMEZ-JERIA, JUAN S¹ 

[1] University of Chile, Santiago, Chile

关键词: Hepatitis C virus;    QSAR;    NS5B polymerase;    Quantum Pharmacology;    Quantum Chemistry;    HCV replicons.;   

DOI  :  10.4067/S0717-97072013000400055

学科分类：化学（综合）

来源: Sociedad Chilena de Quimica

【 摘 要 】

This paper uses newly developed and extended quantum chemical methods in an attempt to advance the knowledge of the relationship between the variation of several local atomic descriptors of the electronic structure and the variation of the inhibitory capacity of a group of reversible and irreversible inhibitors of hepatitis C virus NS5B polymerase. Good structure-activity relationships were obtained for both kinds of compounds. Some processes are charge-, orbital- and/or steric-controlled. The action mechanisms seem to be different for reversible and irreversible inhibitors. Also, good QSAR equations were obtained for the activities of these compounds in a cellular replicon assay and for pharmacokinetic profiles. The local atomic hardness seems to give a good account of the interaction of the drugs with apolar sites of the partner (enzyme, receptor, etc.). This is the first time that a purely quantum-chemical index is able to deal directly with this kind of interaction.

【 授权许可】

Unknown