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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(3 H )‐ones as NMDA receptor inhibitor
Author(s) -
Saravanan Govindaraj,
Panneerselvam Theivendren,
Kunjiappan Selvaraj,
Parasuraman Pavadai,
Alagarsamy Veerachamy,
Udayakumar Padmaja,
Soundararajan Muthukrishnan,
Joshi Shrinivas D.,
Ramalingam Suresh,
Ammunje Damodar Nayak
Publication year - 2019
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.21511
Subject(s) - chemistry , stereochemistry , in silico , toxicity , metabolism , pharmacology , biochemistry , organic chemistry , medicine , gene
Hit, Lead & Candidate DiscoveryA variety of novel 2‐(methyl/phenyl)‐3‐(4‐(5‐substituted‐1,3,4‐oxadiazol‐2‐yl)phenyl) quinazolin‐4(3 H )‐ones have been synthesized by treating 3‐(4‐(5‐mercapto‐1,3,4‐oxadiazol‐2‐yl)phenyl)‐2‐(methyl/phenyl)‐quinazolin‐4(3 H )‐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 sc PTZ 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 sc PTZ 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 sc PTZ 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.