Title:Computational Study and Synthesis of a New Class of Anticonvulsants with 6 Hz Psychomotor Seizure Test Activity: 2-(1,3-benzodioxol-5-yloxy)- N'-[substituted]-acetohydrazides
Volume: 17
Issue: 10
Author(s): Praveen Kumar*Laxmi Tripathi
Affiliation:
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Uttar Pradesh University of Medical Sciences, Saifai, Etawah- 206130, Uttar Pradesh,India
Keywords:
2-(1, 3-benzodioxol-5-yloxy)-N'-[substituted]-acetohydrazides, computational study, docking, synthesis, 6 Hz psychomotor
seizure test, neurotoxicity.
Abstract:
Background: About 50 million epileptic cases worldwide and 12 million in India are reported.
Currently, available drugs yield adequate control of seizure in 60-70% of patients and show
many toxic effects. These actualities provoked the search for novel, more efficacious and safer anticonvulsants.
Objective: The concatenation of 2-(1,3-benzodioxol-5-yloxy)-N'-[substituted]-acetohydrazides SA 1-
10 was designed by molecular hybridization, optimized by computational study and synthesized with
the objective of obtaining a prototype of potent anticonvulsant molecules especially active against
partial seizures.
Methods: Computational study was performed to calculate the pharmacophoric design, projection of
the pharmacokinetic parameters and docking scores of the titled compounds with molecular targets of
epilepsy. The anticonvulsant activity was ascertained by 6 Hz psychomotor seizure test. Minimal
motor impairment showing neurotoxicity was assessed using the Rotarod test.
Results: Titled compounds possessed the indispensable elements of pharmacophore and displayed
good binding affinity with molecular targets of epilepsy, such as GABA (A) alpha-1 & delta receptor,
glutamate receptor, Na+/H+ exchanger and GABA- aminotransferase in docking studies. The most
potent compound of the concatenation was 2-(1,3-benzodioxol-5-yloxy)-N'-[4-(4-
chlorophenoxy)benzylidene]-acetohydrazide SA 4, showing 100% protection at four different time
points with ED50 value 146.8 mg/kg at a TPE of 1 h in mice.
Conclusion: The protection shown in 6 Hz test is implicated as the compound's ability to control
partial seizures. Thus, the titled compounds can be considered as potential prototype candidates for
antiepileptic therapy against partial seizures.
