Title:Synthesis, Molecular Docking and Evaluation of 3-{4-[2-amino-4-(substitutedphenyl)-2H-[1, 3] oxazin/thiazin-6-yl} 2-phenyl-3H-quinazolin-4-one Derivatives for their Anticonvulsant Activity
VOLUME: 18 ISSUE: 1
Author(s):Nimisha Jain, Jugnu Jaiswal, Ashish Pathak and Pradeep K. Singour*
Affiliation:Computational & Synthetic Chemistry Division, Department of Pharmaceutical Chemistry, VNS Group of Institutions- Faculty of Pharmacy, Neelbud, Bhopal- 462023 (M.P.), Computational & Synthetic Chemistry Division, Department of Pharmaceutical Chemistry, VNS Group of Institutions- Faculty of Pharmacy, Neelbud, Bhopal- 462023 (M.P.), Computational & Synthetic Chemistry Department, Ravishankar college of Pharmacy, Bhopal-462044 (M.P.), Computational & Synthetic Chemistry Division, Department of Pharmaceutical Chemistry, VNS Group of Institutions- Faculty of Pharmacy, Neelbud, Bhopal- 462023 (M.P.)
Keywords:Anticonvulsant, GABAA, MES, quinazolin-4(3H)-ones, scPTZ, seizures.
Abstract:Background: According to the WHO, around 50 million people worldwide are suffering
from epilepsy. It is due to the repeated occurring of seizures. These seizures are caused by sudden
which may vary from a brief lapse of attention or muscle jerks, to severe and prolonged convulsions.
Objectives: The aim of the present work was to synthesize 2-phenyl substituted quinazolinone derivatives
and to evaluate them for anticonvulsant and neurotoxic activity.
Methods: A series of novel 3-{4-[2-amino-4-(substitutedphenyl)-2H-[1.3] oxazin/thiazin-6-yl} 2-
phenyl-3H-quinazolin-4-one derivatives were synthesized and evaluated for their anticonvulsant activity.
The structures of the compound have been confirmed by spectral analysis. The molecular docking
was performed for all the synthesized compounds to assess their binding mode to Gamma- aminobutyric
acid type A (GABAA) receptor in order to rationalize their anticonvulsant activities in a qualitative way.
Anticonvulsant activities of compounds were screened by using (Maximal electroshock) MES induced
seizures and subcutaneous pentylenetetrazole (scPTZ) induced seizure models in Wistar rats of either
sex. None of the compounds demonstrated any sign of neurotoxicity.
Result: Compounds 3-{4-[2-amino-4-(4-nitro-phenyl)-2H-[1, 3] oxazin-6-yl} 2-phenyl-3H-quinazolin-
4-one (5a) have shown significant activity against tonic seizure by the MES model and 3-{4-[2-amino-
4-(4-nitro-phenyl)-2H-[1, 3] thiazin-6-yl} 2-phenyl-3H-quinazolin-4-one (5d) against clonic seizure by
scPTZ induced seizure model.
Conclusion: All the newly synthesized compounds had significant anticonvulsant activity. The same
two compounds 5a and 5d showed promising activity, while the other compounds have moderate activity.
The proposed work is to effort towards the development and identification of novel molecules as
anticonvulsant agents by the synthesis of some novel quinazolinone derivatives with improved biological
activity.
