A computational study on conformational geometries, chemical reactivity and inhibitor property of an alkaloid bicuculline with γ-aminobutyric acid (GABA) by DFT

• Published in: Computational and theoretical chemistry 2012-08, Vol.993, p.80-89
• Main Authors: Srivastava, Anubha, Rawat, Poonam, Tandon, Poonam, Singh, R.N.
• Format: Article
• Language: English
• Subjects: Bicuculline; DFT method; Fukui function; GABA receptor; HOMO–LUMO
• ISSN: 2210-271X
• DOI: 10.1016/j.comptc.2012.05.025

[Display omitted] ► The equilibrium bicuculline conformers have been obtained by geometry optimizations using DFT. ► The antagonistic behavior of bicuculline with GABA receptor have been evaluated using 6-311G(d,p) basis. ► The specific site of interaction of BIC with GABA receptor have been calculated. ► The global and local reactivity descriptors of BIC and GABA have been discussed. ► Condensed Fukui functions and HOMO–LUMO gap for bicuculline and GABA receptor are computed. Bicuculline – a plant alkaloid is an important molecule of current pharmaceutical interest. It is a competitive antagonist of γ-aminobutyric acid (GABA), particularly of GABAA receptor activation. The antagonistic behavior of BIC with GABAA receptor has been evaluated with the help of quantum chemical calculations. The equilibrium structures of bicuculline conformers have been obtained by geometry optimizations using density functional theory (DFT) calculations at the B3LYP/6-311G(d,p) level of theory. The conformational flexibility of bicuculline has been investigated because of its importance as an apparently specific antagonist of the neurotransmitter GABA. Dipole moment and first hyperpolarizability analysis of BIC have also been performed. For predicting inhibitor properties of BIC, the specific site of interaction of BIC with GABA receptor has been calculated with the help of global and local reactivity descriptors using DFT. Condensed Fukui functions, relative nucleophilicity and electrophilicity indices of BIC and GABA receptor for electrophilic or nucleophilic attack, are computed and compared with the HOMO and LUMO densities, integrated over the Hirshfeld atoms in molecules.