Synthesis of some noval qunazolinone derivatives for their anticonvulsant activity

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INTRODUCTION
Quinazolinone derivatives have emerged as a class of compounds with versatile biological activities, drawing considerable interest in medicinal chemistry.The broad spectrum of biological properties associated with quinazolinones, coupled with their structural diversity, has positioned them as promising candidates for drug development [1][2][3] .In particular, quinazolinone derivatives have exhibited a myriad of pharmacological effects, including anticancer 4 , antimicrobial 5 , antifungal 6 , antiviral 7 , antitumer 8 , antimalarial 9 , muscle relaxant 10 , anti-inflammatory 11 , anti-tubercular 12 , and anticonvulsant 13 activities, among others.The focus of this study is the synthesis of novel quinazolinone derivatives designed with the specific aim of evaluating their potential anticonvulsant activity.Epilepsy, a neurological disorder characterized by recurrent seizures, remains a significant global health concern.Despite advancements in treatment options, there is a continuous need for the discovery of new and more effective anticonvulsant agents [14][15][16][17] .This research contributes to the ongoing efforts in medicinal chemistry to explore diverse chemical structures for their therapeutic potential.By synthesizing and evaluating novel quinazolinone derivatives, we aim to expand the understanding of their anticonvulsant properties, paving the way for the development of new drugs to address the challenges associated with epilepsy.The investigation involves not only the synthesis of these compounds but also their comprehensive characterization and evaluation using established preclinical models, such as the Maximal Electroshock (MES) method.The outcomes of this research hold the promise of advancing our knowledge in the pursuit of innovative treatments for neurological disorders, with a particular focus on anticonvulsant interventions.

Method and Scheme
Quinazolines were studied using the synthetic method. 18ep-I Synthesis Anthranillic acid or substituted anthranillic acid (0.1M) was dissolved in 60 mL pyridine and then added benzoyl chloride (0.05M) drop wised and stirring the product half an hour and neutralize the product with NaHCo 3 , recrystallized with ethanol.'Tempo' melting point equipment was used to determine the melting point, and the results were uncorrected.There were also melting points.

Anticonvulsant activity determination
Using the MES (maximal electroshock) method, we conducted assessments on the anticonvulsant activity of all synthesized compounds.Swiss albino mice, weighing between 20 and 35 g and sourced from Bhubaneshwar, were employed in the study.The animal facility maintained a 12:12 h light/dark cycle, a room temperature of 24°C, humidity levels between 45% and 55%, and adhered to stringent hygiene standards for water supply.Prior to experimentation, the Institutional Animal Ethical Committee (IAEC) of SOA University Bhubaneswar granted approval in accordance with the ethical guidelines outlined by the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), registration number 1171/c/08/ (CPCSEA).Methodology involved the formation of three groups of male albino mice, each weighing 20-30 g, with six animals in each group.The groups received different treatments: a control group (3% saline), a standard medicine group (phenytoin 25 mg/kg), and a group administered with the synthesized substance.For the experimental technique, mice were subjected to a 0.2-second electrical stimulus via small alligator clips attached to the cornea.A rectangular plastic cage with an open top was used for housing mice during the test session, allowing the recording of various parameters and full visibility of the animal's motor reactions to seizures.During the 30-min testing period, parameters such as clonus convulsions, tonic flexion, tonic extension, stupor, and the percentage of protection were recorded.Mean SEM values were calculated from the results of six animals.Statistical analysis involved ANOVA and Dunnett's t-test to determine any significant differences between the groups, with a significance level set at P<0.05.19,20

RESULT AND DISCUSSION
The synthesis of novel quinazolinone derivatives was achieved through a systematic multi-step process, involving the condensation of appropriate precursors.The structures of the synthesized compounds were confirmed through comprehensive spectroscopic characterization, including NMR and mass spectrometry.The successful synthesis of these compounds provided a solid foundation for further investigation into their pharmacological activities.The anticonvulsant potential of the synthesized quinazolinone derivatives was assessed using the Maximal Electroshock (MES) method, a standard preclinical model for screening antiepileptic drugs.[23][24] A glance at the table, which lists the antiseizure activity and associated structures, reveals that almost all of the drugs are active."The values are IR (KBr in cm -   [25][26][27] The compounds B-4 and A-3, which were the least active, had the following chemical structures.
If we compare the structures of the produced compounds to their activities, we observe that the R' group of the =C6H5-R' should be substituted at position -4 of the ring.The activity is at its highest when the substitution is R=H, R'=H relative to other substituent's.

The compound's structure which gave the best activity is
The unsubstituted compound showed the maximum activity then substituted compounds.

CONCLUSION
In conclusion, the synthesis and evaluation of novel quinazolinone derivatives for their anticonvulsant activity have yielded significant insights into their potential therapeutic applications.The diverse biological properties historically associated with quinazolinones have been further extended by the discovery of promising anticonvulsant effects in our study.The Maximal Electroshock (MES) method served as a robust preclinical model to assess the efficacy of the synthesized compounds in mitigating seizures.The observed anticonvulsant activity of select quinazolinone derivatives underscores their potential as candidates for further development in the treatment of epilepsy.The structure-activity relationships deduced from this research provide a foundation for future medicinal chemistry endeavors.Understanding the specific structural features that contribute to anticonvulsant effects is crucial for the rational design of more potent and selective compounds.Additionally, further studies exploring the mechanisms of action, pharmacokinetics, and safety profiles of these derivatives will be essential for their progression toward clinical applications.