Molecules, Vol. 29, Pages 1951: Synthesis, In Vivo Anticonvulsant Activity Evaluation and In Silico Studies of Some Quinazolin-4(3H)-one Derivatives

Molecules, Vol. 29, Pages 1951: Synthesis, In Vivo Anticonvulsant Activity Evaluation and In Silico Studies of Some Quinazolin-4(3H)-one Derivatives Molecules doi: 10.3390/molecules29091951 Authors: Raluca Pele Gabriel Marc Cristina Mogoșan Anamaria Apan Ioana Ionuț Brîndușa Tiperciuc Cristina Moldovan Cătălin Araniciu Ilioara Oniga Adrian Pîrnău Laurian Vlase Ovidiu Oniga 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 pentylenetetraz...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research