Journal of Advanced Pharmaceutical Technology & Research

ORIGINAL ARTICLE
Year
: 2015  |  Volume : 6  |  Issue : 2  |  Page : 65--74

New avenue in the treatment of temporal lobe epilepsy by classical anti-epileptics: A hypothetical establishment of executioner Caspase 3 inactivation by molecular modeling


M Vijey Aanandhi1, Debojit Bhattacherjee1, Anirban Ray2, P Samuel Gideon George1 
1 Department of Pharmaceutical Chemistry and Pharmacy Practice, School of Pharmaceutical Sciences, Vels University (VISTAS), Chennai, Tamil Nadu, India
2 Department of Pharmacology, Roland Institute of Pharmaceutical Sciences, Khodasingi, Berhampur, India

Correspondence Address:
M Vijey Aanandhi
Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Vels University (VISTAS), Chennai - 600 117, Tamil Nadu
India

Patients with temporal lobe epilepsy (TLE) are prescribed first-line antiepileptic drugs and surgery to the management of this disorder. Unfortunately, the surgical treatment has been shown to be beneficial for the selected patients but fails to provide a seizure-free outcome in 20-30% of TLE patients. In our present study, we investigate the possibilities of marketed antiepileptic drugs in a different manner to improve the present situation in TLE. Molecular docking simulation study and various open source computational tools were used to perform the study. AutoDock 4.2 MGL tools, Pymol visualize tools, Patch dock server, and Swarm Dock servers (protein-protein docking) were used to perform the molecular modeling. FTsite and computed atlas of surface topography of protein open source server were used to understand the pocket and ligand binding information respectively. Toxtree application was used to determine the toxicity profile of the drug by Cramers rule. The obtained molecular docking models (Caspase 3, Procaspase 8, and Fas-associated death domain [FADD]) with selected compounds (Clonazepam, Clobazepam, and Retigabine) showed promising trio blocking event of FADD, Caspase 3, and Procaspase 8 (−6.66 kcal, −8.1 kcal, 6.46 kcal) by Clonazepam respectively. Protein-protein interaction study (Swarm Dock, Patch Dock server) indicated promising results that helped to establish our hypothesis. Toxtree showed a quantitative structure toxicity relationship report that helps to clarify the toxicity of the selected compounds. Clonazepam showed a trio inhibition property that may lead to develop a new era of the new generation benzodiazepine prototype drugs in the future. Filtered compounds will further process for higher in vitro, in vivo models for better understanding of the mechanism.


How to cite this article:
Aanandhi M V, Bhattacherjee D, Ray A, George P S. New avenue in the treatment of temporal lobe epilepsy by classical anti-epileptics: A hypothetical establishment of executioner Caspase 3 inactivation by molecular modeling.J Adv Pharm Technol Res 2015;6:65-74


How to cite this URL:
Aanandhi M V, Bhattacherjee D, Ray A, George P S. New avenue in the treatment of temporal lobe epilepsy by classical anti-epileptics: A hypothetical establishment of executioner Caspase 3 inactivation by molecular modeling. J Adv Pharm Technol Res [serial online] 2015 [cited 2021 Feb 26 ];6:65-74
Available from: https://www.japtr.org/article.asp?issn=2231-4040;year=2015;volume=6;issue=2;spage=65;epage=74;aulast=Aanandhi;type=0