Stability Index Based Quantitative Structure-Activity Relationship Study of β-Carbolines

Abstract

Quantitative structure-activity relationship (QSAR) study of derivatives of β-carboline has been made with the help of quantum chemical parameter: stability index (HOMO-LUMO gap). For QSAR study, the molecular modeling and geometry optimization for all the derivatives were carried out with CAChe Pro software and the HOMO/LUMO energies were evaluated by a MOPAC/PM3 wave function for the chemical sample, at a geometry determined by MOPAC using PM3 parameters. The study has shown that there is inverse relationship between stability index and observed biological activity i.e., as stability index increases reactivity of the β-carboline derivatives decrease because a large HOMO-LUMO gap implies high stability for the molecule in the sense of its lower reactivity in chemical reactions. Thus stability index provides valuable information to explore the interaction of β-carboline with the receptor and to distinguish between the agonistic, antagonistic and inverse agonistic activities of the ligands.