Synthesis, characterization, anxiolytic and anticonvulsant activity, DFT, molecular docking, DMPK studies of chalcone derived from maleic anhydride

Anxiety typically doesn't cause convulsions, but intense stress can reduce the threshold for convulsive bouts in predisposed individuals. Chalcones are known to act directly on the central nervous system (CNS) and the presence of electron donor and acceptor groups attached to the aromatic rings in various positions can alter the properties of the molecule. Thus, this work investigated the anxiolytic and anticonvulsant potential of the new chalcone derivative (E)-6-(4-((E)-3-(3-nitrophenyl)acryloyl)phenyl)-5-oxohex-2-enoic acid (CAMEL). ¹H and ¹³C NMR and ATR-FTIR analyses helped to determine the molecular structure of this chalcone. The energy gap analysis and the higher hardness values than the softness values confirm the stability of CAMEL, with CGDRs indicating that it is more electrophilic in nature. In relation to its potential anxiolytic effect, the tested dose of 40 mg kg^-1 of the derivative showed behavior like Diazepam, with activity via GABAA. In addition, the derivative also exhibited a possible anticonvulsant effect at the dose of 20 mg kg^-1, being like Diazepam, showing involvement in stages 2 and 3 of GABAA receptors in this process. Given the anxiolytic and anticonvulsant activity shown in vivo and in silico tests, CAMEL is a promising candidate for the treatment of diseases that affect the CNS.