Graph theoretical analysis, in silico modeling, prediction of toxicity, metabolism and synthesis of novel 2-(methyl/phenyl)-3-(4-(5-substituted-1,3,4-oxadiazol-2-yl) phenyl) quinazolin-4(3H)-ones as NMDA receptor inhibitor.

Autor: Saravanan G; Department of Pharmaceutical Chemistry, MNR College of Pharmacy, Sangareddy, Telangana, India., Panneerselvam T; Department of Pharmaceutical Chemistry, Karavali College of Pharmacy, Mangalore, Karnataka, India., Kunjiappan S; International Research Center, Kalasalingam University, Krishnan Koil, Tamil Nadu, India., Parasuraman P; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, M. S. Ramaiah University of Applied Sciences, Bengaluru, Karnataka, India., Alagarsamy V; Department of Pharmaceutical Chemistry, MNR College of Pharmacy, Sangareddy, Telangana, India., Udayakumar P; Department of Pharmacology, Father Muller Medical College, Mangalore, Karnataka, India., Soundararajan M; Department of Pharmaceutical Chemistry, Karavali College of Pharmacy, Mangalore, Karnataka, India.; Department of Pharmacology, Karavali College of Pharmacy, Mangalore, Karnataka, India., Joshi SD; Department of Pharmaceutical Chemistry, Sonia Education Trust's College of Pharmacy, Dharwad, Karnataka, India., Ramalingam S; Department of Pharmacy, Annamalai University, Chidambaram, Tamil Nadu, India., Ammunje DN; Department of Pharmacology, Faculty of Pharmacy, M. S. Ramaiah University of Applied Sciences, Bengaluru, Karnataka, India.
Jazyk: angličtina
Zdroj: Drug development research [Drug Dev Res] 2019 May; Vol. 80 (3), pp. 368-385. Date of Electronic Publication: 2019 Jan 04.
DOI: 10.1002/ddr.21511
Abstrakt: 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.
(© 2019 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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