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

Abstract

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.

An In Silico Molecular Modelling-Based Prediction of Potential Keap1 Inhibitors from Hemidesmus indicus (L.) R.Br. against Oxidative-Stress-Induced Diseases

“…Using the optimized structures, the frontier molecular orbital energies of the chosen bioactive compounds were determined, including their energy gaps (Eg) and lowest unoccupied molecular orbitals (ELUMO) and highest occupied molecular orbitals (EHOMO). GaussView, a molecular visualization programme, was used to depict the molecular orbital energy diagrams that were produced for the chosen bioactive chemicals [69].…”

Design and Synthesis of Novel 1-substituted-3-(3-(3-nitrophenyl)-4-oxo-3,4-dihydrobenzopyrimidin-2-yl amino) Isothioureas for their Anti-HIV, Antibacterial Activities, Graph Theoretical Analysis, Insilico Modeling, Prediction of Toxicity and Metabolic Studies

“…Kyoto encyclopedia of genes and genomes database was utilized for the study of graph theoretical analysis. The influential proteins was recognized and chosen by network of protein interaction (mtu: 00770) in homo sapiens [25][26][27][28].…”