Your browser doesn't support javascript.
loading
Synthesis, In Vivo Anticonvulsant Activity Evaluation and In Silico Studies of Some Quinazolin-4(3H)-One Derivatives.
Pele, Raluca; Marc, Gabriel; Mogoșan, Cristina; Apan, Anamaria; Ionuț, Ioana; Tiperciuc, Brîndușa; Moldovan, Cristina; Araniciu, Catalin; Oniga, Ilioara; Pîrnau, Adrian; Vlase, Laurian; Oniga, Ovidiu.
Affiliation
  • Pele R; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, "Iuliu Hațieganu" University of Medicine and Pharmacy, 41 Victor Babeș Street, 400012 Cluj-Napoca, Romania.
  • Marc G; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, "Iuliu Hațieganu" University of Medicine and Pharmacy, 41 Victor Babeș Street, 400012 Cluj-Napoca, Romania.
  • Mogoșan C; Department of Pharmacology, Physiology and Pathophysiology, Faculty of Pharmacy, "Iuliu Hațieganu" University of Medicine and Pharmacy, 6A Louis Pasteur Street, 400349 Cluj-Napoca, Romania.
  • Apan A; Department of Pharmacology, Physiology and Pathophysiology, Faculty of Pharmacy, "Iuliu Hațieganu" University of Medicine and Pharmacy, 6A Louis Pasteur Street, 400349 Cluj-Napoca, Romania.
  • Ionuț I; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, "Iuliu Hațieganu" University of Medicine and Pharmacy, 41 Victor Babeș Street, 400012 Cluj-Napoca, Romania.
  • Tiperciuc B; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, "Iuliu Hațieganu" University of Medicine and Pharmacy, 41 Victor Babeș Street, 400012 Cluj-Napoca, Romania.
  • Moldovan C; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, "Iuliu Hațieganu" University of Medicine and Pharmacy, 41 Victor Babeș Street, 400012 Cluj-Napoca, Romania.
  • Araniciu C; Department of Therapeutical Chemistry, Faculty of Pharmacy, "Iuliu Hațieganu" University of Medicine and Pharmacy, 12 Ion Creanga, 400010 Cluj-Napoca, Romania.
  • Oniga I; Department of Pharmacognosy, "Iuliu Hațieganu" University of Medicine and Pharmacy, 12 Ion Creanga, 400010 Cluj-Napoca, Romania.
  • Pîrnau A; National Institute for Research and Development of Isotopic and Molecular Technologies, 67-103 Donat Street, 400293 Cluj-Napoca, Romania.
  • Vlase L; Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, "Iuliu Hațieganu" University of Medicine and Pharmacy, 41 Victor Babeș Street, 400012 Cluj-Napoca, Romania.
  • Oniga O; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, "Iuliu Hațieganu" University of Medicine and Pharmacy, 41 Victor Babeș Street, 400012 Cluj-Napoca, Romania.
Molecules ; 29(9)2024 Apr 24.
Article in En | MEDLINE | ID: mdl-38731442
ABSTRACT
Two series, "a" and "b", each consisting of nine chemical compounds, with 2,3-disubstituted quinazolin-4(3H)-one scaffold, were synthesized and evaluated for their anticonvulsant activity. They were investigated as dual potential positive allosteric modulators of the GABAA receptor at the benzodiazepine binding site and inhibitors of carbonic anhydrase II. Quinazolin-4(3H)-one derivatives were evaluated in vivo (D1-3 = 50, 100, 150 mg/kg, administered intraperitoneally) using the pentylenetetrazole (PTZ)-induced seizure model in mice, with phenobarbital and diazepam, as reference anticonvulsant agents. The in silico studies suggested the compounds act as anticonvulsants by binding on the allosteric site of GABAA receptor and not by inhibiting the carbonic anhydrase II, because the ligands-carbonic anhydrase II predicted complexes were unstable in the molecular dynamics simulations. The mechanism targeting GABAA receptor was confirmed through the in vivo flumazenil antagonism assay. The pentylenetetrazole experimental anticonvulsant model indicated that the tested compounds, 1a-9a and 1b-9b, present a potential anticonvulsant activity. The evaluation, considering the percentage of protection against PTZ, latency until the onset of the first seizure, and reduction in the number of seizures, revealed more favorable results for the "b" series, particularly for compound 8b.
Subject(s)
Key words

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pentylenetetrazole / Seizures / Receptors, GABA-A / Anticonvulsants Limits: Animals Language: En Journal: Molecules Journal subject: BIOLOGIA Year: 2024 Document type: Article Affiliation country: Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pentylenetetrazole / Seizures / Receptors, GABA-A / Anticonvulsants Limits: Animals Language: En Journal: Molecules Journal subject: BIOLOGIA Year: 2024 Document type: Article Affiliation country: Country of publication: