DESIGN AND SYNTHESIS OF NOVEL HYDRAZONES OF ETHYL3-AMINO-4-HYDROXYBENZOATE AS PROMISING ANTICONVULSANT AGENTSAbstract
A series of hydrazide-hydrazones (3a-o) have been synthesized by the reaction of acid hydrazide (2) which is obtained from 4-carbomethoxy-2-aminophenol with aromatic acid through multi-steps. The bioactivities of the final compounds were tested with MES and scPTZ methods. The CNS toxicity was studied by the rotarod experiment. Based on the results, compounds 3d and 3o were found to be most active at 30 mgkg-1 in the MES test with prolonged duration of action; they exhibited activity comparable to standard drugs phenytoin and carbamazepine. Compounds 3f, 3j and 3m exposed toxicity (300 mgkg-1) at 0.5 h of the time period and compounds 3i, 3n and 3o exhibited late toxicity after 4.0 h as compared to carbamazepine. The rest of the compounds did not face toxicity at a maximum dose level (300 mgkg-1). This study shows that increased lipophilicity is directly related to the anticonvulsant activity. Further studies need to be carried out on other seizure tests and models of epilepsy to ascertain the precise mechanism of action of these molecules.
M. Sarafroz *, Y. Khatoon, N. Ahmad, M. Amir, Salahuddin, F. H. Pottoo, M. Taleuzzaman and W. Ahmad
Department of Pharmaceutical Chemistry, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, City Dammam, Saudi Arabia.
01 April 2019
09 November 2019
24 December 2019
01 January 2020