Synthesis and Evaluation of Anticonvulsant Activity of New 2-(4-Oxo-2-Propylquinazolin-4(3H)-yl) Acetohydrazide Derivatives

Aim: A new series of 2-(4-oxo-2-propylquinazolin-4(3H)-yl)acetohydrazide derivatives was prepared by reacting quinazolin-4(3H)-one hydrazide with substituted aromatic aldehydes. Quinazoline is a powerful pharmacological drug that possesses a number of biological properties, including antibacterial, antiviral, anticancer, convulsive, anxiety-inducing, anti-inflammatory, and analgesic properties. In this background, we have synthesized a series of quinazoline 4(3H)-one derivative 4a-4f and screened for their anticonvulsant activity.

Background: Antiepileptic agents are neither curative nor preventive and are active exclusively as a means of controlling the symptoms of epilepsy. They can directly act on ion channels or indirectly impact the synthesis, metabolism, or function of neurotransmitters or receptors that control channel opening and closing.

Methods: In this work, Schiff bases were prepared by treating quinazolin-4(3H)-one hydrazide with aromatic aldehydes. Six compounds 4a-4f were screened for anticonvulsant activity using the Isoniazid (INH)- and Pentylenetetrazole (PTZ)-induced convulsion models in mice.

Results: All the compounds were given satisfactory reaction yields that represent the efficiency of the employed synthetic route. In the INH-induced convulsion model, quinazolinones 4a, 4b, 4d, 4e, and 4f significantly delayed the onset of convulsion when compared to an induction control group, while the delay in seizure onset was not significant for 4c. In the PTZ-induced convulsion model, quinazolinones 4a, 4d, 4e, and 4f considerably delayed the onset of convulsion when compared to the induction control group, while the delay in seizure onset was not significant for 4b and 4c.

This indicates the anticonvulsant activity of these derivatives which might be due to potentiating GABA activity in the CNS. This anticonvulsant activity was due to the presence of electron-donating groups like OH, NH2, and OCH3 and electron-withdrawing groups like CF3 at the 2nd and 4th positions of the aromatic ring attached to the hydrazide function.

Conclusion: Based on the results, it can be concluded that quinazoline-4(3H)-one derivative exhibited anticonvulsant activity. Notably, all tested compounds showed prolonged onset of convulsions and protected maximum animals, suggesting an increased level of GABA by its potentiation or prevention of its depletion.