title: Synthesis, in silico metabolic and toxicity prediction of some novel imidazolinones derivatives as potent anticonvulsant agents.
abstract: A series of 1,2,4-trisubstituted 5-imidazolinone derivatives were synthesized by Erlenmeyer condensation of benzoylglycine (hippuric acid) with different aldehydes in the presence of sodium acetate and acetic anhydride. The derivatives of the compounds were prepared by condensation of some known sulpha drugs with 5-oxazolone derivatives. The anticonvulsant activity of the compounds was determined by the protection of pentylenetetrazole-induced convulsions that was ranged from 10 to 60%. The compounds with p-OCH₃, p-OH and o-Cl substitutions in the phenyl ring on 4(th) position of the imidazolinone ring exhibited good anticonvulsant activity. In silico metabolic and toxicity studies showed that all the compounds in the series are not likely to exhibit toxicity except the compounds IIIa, IIIb, VIa and VIb, that is predicted to show 29% mutagenicity and 53% irritation in comparison to the other compounds. The predicted lethal effect and hERG toxicity of the compounds showed that IIa, IVa, Va and Vb might be toxic at higher concentrations. The results successfully establish the synthesized imidazolinone derivatives as novel compounds with anticonvulsant properties, low predicted cardiotoxicity and lethal effects thus can be promising leads for further development as novel anticonvulsants.
authors.affiliation: School of Pharmaceutical Sciences , Rajiv Gandhi Proudyogiki Vishwavidyalaya, Gandhi Nagar, Bhopal, India. nshnm06@yahoo.co.in
authors.forename: N S Hari Narayana
authors.initials: NS
authors.lastname: Moorthy
authors.forename: Vipin
authors.initials: V
authors.lastname: Saxena
authors.forename: C
authors.initials: C
authors.lastname: Karthikeyan
authors.forename: Piyush
authors.initials: P
authors.lastname: Trivedi
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity*; D003292:Convulsants / Q000633:toxicity; D048288:Imidazolines / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity*; D051379:Mice; D015394:Molecular Structure; D010433:Pentylenetetrazole / Q000633:toxicity; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D012984:Software; D013329:Structure-Activity Relationship
chemical_list: D000927:Anticonvulsants; D003292:Convulsants; D048288:Imidazolines; D010433:Pentylenetetrazole