In-silico comparative study of three (3) bioactive compounds from methanol extracts of Combretum micranthum leaf, and diazepam with Gabaa receptor molecule

Abstract

Stress affects monoamine neurotransmitter in the central nervous system such as GABA (a major inhibitory neurotransmitter in the brain). GABA_A receptor is hetero-oligomeric Cl-channel that is elective blocked by the alkaloid, bicuculline and modulated by steroids, barbiturates and benzodiazepines. The anticonvulsant activity of Diazepam may be mediated by enhancement of inhibition involving gamma-aminobutyric acid (GABA). Combretum micranthum is one of the maximum effective medicinal plants of therapeutic importance. Thus this study is to examine the effect of Combretum micranthum methanol leaf extract on GABA_A Receptor via In-Silico analysis. Combretum micranthum methanol leaf extract was found using GC-MS to contain bioactive compounds (3,5-dichlorophenylhydrazine, guanidine and aminooxyacetic acid) with GABAergic functions. And the popular docking programs PatchDock and AutoDockVina were then used to predict computationally binding modes of these compounds with GABA_A receptor. The molecular docking analyses indicated highly and effectively interactions (binding energy in kcal/mol) between GABA_A receptor and the Combretum micranthum compounds (ligands): 3,5-dichlorophenylhydrazine (-193.85 and-5.6), guanidine (-87.63 and -3.3) and aminooxyacetic acid (-85.3 and -3.2) for both PatchDock and AutoDock Vina respectively. Results shows that 3,5-dichlorophenylhydrazine has a close binding energy in kcal/mol to that of Diazepam (-200.68 and -6.1 respectively). Findings of the study shows that the interaction between Combretum micranthum compounds (3,5-dichlorophenylhydrazine, guanidine and aminooxyacetic acid) with GABA_A receptor can be explore for the development of new therapeutics to manage mental disorders.  

Keywords: Gamma-aminobutyric acid, Combretum micranthum , AutoDockVina, PatchDock