In silico Design, Synthesis and Pharmacological screening of Quinazolinones as NMDA receptor antagonists for Anticonvulsant activity: Part II

Abstract

Background: N-methyl-D-Aspartate (NMDA) receptor plays a main role in eliptogenisis and its inhibition has therapeutic significance in development of anticonvulsants. Prioritized quinazolinone molecules were synthesized, evaluated in vivo by AOT and then for anticonvulsant activity in NMDA induced convulsion model.Method: In silico Screening of prioritized molecule was done by biological activity predictions, partition coefficient predictions (Log P), molecular docking on NMDA receptors, in silico ADME predictions using PASS server and mol inspiration software, V Life MDS 4.3 software and Pre ADMET server respectively. This gave biological activity (BA) score for anticonvulsant activity and predicted Log P values (p Log P). The standard Log P required for anticonvulsant activities being more than 2.00, therefore molecules were also prioritized based on this p Log P criteria. Docking showed results of antagonism in silico as compared with Memnatine and molecules were prioritized for synthesis based on this criteria.Result: Quinazolinone molecules were prioritized based upon docking score, ADME and BA score, synthesized and pharmacologically screened for anticonvulsant activity.Conclusion: SMMB1, SMMB2, SMMB3 showed the prominent anticonvulsant activity as compared with memantine used as standard for in vivo anticonvulsant activity. The compounds can serve as anticonvulsant Leads through NMDA antagonism.

Keywords: Anticovulsant; Mol inspiration; NMDA; PASS; Pre ADMET; Quinazolinone