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Hit, Lead & Candidate Discovery A variety of novel 2-(methyl/phenyl)-3-(4-(5-substituted-1,3,4-oxadiazol-2-yl)phenyl) quinazolin-4(3H)-ones have been synthesized by treating 3-(4-(5-mercapto-1,3,4-oxadiazol-2-yl)phenyl)-2-(methyl/phenyl)-quinazolin-4(3H)-one with a variety of secondary amines. Graph theoretical analysis was used in identification of drug target that is, NMDAR (N-methyl-d-aspartate receptors). The observed reports of in silico modeling and ligand based toxicity, metabolism prediction studies were encouraging us to synthesize of title compounds and evaluate their antiepileptic effects. The title compounds were tested for its antiepileptic potency by MES and scPTZ model. Rotorod test is used to assess its neurotoxicity. In the preliminary test it was found that in MES test, analogs 6d, 6e, 6f, and 6l were potent; whereas in scPTZ test analogs 6d, 6e, 6f, and 6k displayed potent antiepileptic activity. Additionally these five derivatives were tested in rats orally at a dose of 30 mg/kg and found that compounds 2-methyl-3-(4-(5-morpholino-1,3,4-oxadiazol-2-yl)phenyl)quinazolin-4(3H)-one 6e and 2-methyl-3-(4-(5-(piperidin-1-yl)-1,3,4-oxadiazol-2-yl)phenyl)quinazolin-4(3H)-one 6f exhibited superior activity than reference Phenytoin. In MES test, these derivatives 6e and 6f showed activity at 30 mg/kg i.p. dose after 0.5 hr and 4.0 hr. In scPTZ test these derivatives 6e and 6f showed activity at 100 and 300 mg/kg i.p. dose after 0.5 hr and 4.0 hr, respectively.

Hit, Lead & Candidate Discovery A series of 2-(2-substituted benzylidenehydrazinyl-2-oxopropyl)-3-(4-[4-oxo-2-phenylthiazolo din-3-yl]phenyl)quinazolin-4(3H)-one 7a-7l were synthesized and characterized by IR, 1 H-NMR, 13 C-NMR, mass spectroscopy and elemental analyses. In this present study, the density functionality theory was performed to identify drug stability. Further we introduced graph theoretical analysis by utilised Kyoto Encyclopedia of Genes and Genomes (KEGG) database and Cytoscape software to identify drug target. Based on the observed drug target insilico modeling was executed to know effective drug. The antiepileptic effects of title compounds were evaluated by using MES and subcutaneous pentylenetetrazole (scPTZ) test. Acute neurological toxicity of title compounds was studied by using standardized rotorod test. After 0.5 hr of period many of the compounds showed anticonvulsant activity at MES or scPTZ test. Comparison of the biological activity of test compounds with its chemical structures indicates that, compounds possessing electron donating group exhibited superior activity than the analogs having electron withdrawing moieties. Among the electron donating group tested, amino derivative exhibited good activity than rest of derivatives. From the study it was concluded that, the compound 7j was established as very potent compared with rest of the compounds and standard drugs subjected to biological studies. Thus the compound 2-(2-[4-aminobenzylidene]hydrazinyl-2-oxopropyl)-3-(4-[4-oxo-2-phenylthiazolidin-3-yl]phenyl) quinazolin-4(3H)-one (7j) came out as pilot derivative without any neurotoxicity with a wide spectrum of antiepileptic activity. HIGHLIGHTS: The performed work is having great significance in terms of Graph theoretical analysis used to identify drug target In silico modeling used to identify designed drug interaction with identify target Density functionality studies used to identify synthesized compound energy band gap which is correlate with enhancement of its biological activity Antiepileptic effects of entire synthesized quinazolinone scaffolds were evaluated by MES and scPTZ test 2-(2-[4-aminobenzylidene]hydrazinyl-2-oxopropyl)-3-(4-[4-oxo-2-phenylthiazolidin-3-yl]phenyl) quinazolin-4(3H)-one (7j) was established as very potent compared to the rest of the compounds and standard drugs which were subjected to biological studies.

A series of novel 1-(substituted benzylidene)-4-(1-(morpholino/piperidino methyl)-2,3-dioxoindolin-5-yl) semicarbazides 6a–6t was designed and synthesized on the basis of semicarbazide-based pharmacophoric model to meet the structural requirements necessary for anticonvulsant activity. The compounds were subjected to in vivo antiepileptic evaluation using maximal electroshock test and subcutaneous pentylenetetrazole seizure test methods. The neurotoxicity was determined by rotorod test. In the preliminary screening, compounds 6c, 6d, 6g, 6h, and 6m were found active in maximal electroshock test model, while 6g, 6i, 6m, and 6o showed significant antiepileptic activity in subcutaneous pentylenetetrazole seizure test model. Further, the compounds 6c, 6d, 6g, 6h, 6i, and 6m were administered orally to rats, of which 6c and 6g showed better activity than phenytoin. Among the synthesized compounds, 6g revealed excellent protection in both models with lower neurotoxicity.