Synthesis and evaluation of 4-substituted semicarbazones of levulinic acid for anticonvulsant activity  

作　　者：AGGARWAL Navneet MISHRA Pradeep 

机构地区：[1]Lachoo Memorial College of Science and Technology, Pharmacy Wing, Jodhpur, Rajasthan 342003, India,Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar, M.P. 470003, India

出　　处：《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》2005年第7期617-621,共5页浙江大学学报（英文版）B辑（生物医学与生物技术）

摘　　要：Objective: A series of 4-aryl substituted semicarbazones of levulinic acid (4-oxo pentanoic acid) was designed and synthesized to meet the structural requirements essential for anticonvulsant activity. Methods: All the compounds were evaluated for anticonvulsant activity. Anticonvulsant activity was determined after intraperitoneal (i.p.) administration to mice by maximal electroshock (MES) and subcutaneous metrazol (ScMet) induced seizure methods and minimal motor impairment was determined by rotorod test. Results: A majority of the compounds exhibited significant anticonvulsant activity after intraperitoneal administration. In the present study 4-(4'-fluoro phenyl) levulinic acid semicarbazone emerged as the most active molecule, showing broad spectrum of activity with low neurotoxicity. Unsubstituted levulinic acid semicarbazone was found to be inactive in all the screens. Conclusion: The results obtained validate the hypothesis that presence of an aryl group near the semicarbazone moiety is essential for anticonvulsant activity. The results also indicate that the hydrophilic-hydrophobic site can accommodate hydrophilic groups.Objective: A series of 4-aryl substituted semicarbazones of levulinic acid (4-oxo pentanoic acid) was designed and synthesized to meet the structural requirements essential for anticonvulsant activity. Methods: All the compounds were evaluated for anticonvulsant activity. Anticonvulsant activity was determined after intraperitoneal (i.p.) administration to mice by maximal electroshock (MES) and subcutaneous metrazol (ScMet) induced seizure methods and minimal motor impairment was determined by rotorod test. Results: A majority of the compounds exhibited significant anticonvulsant activity after intraperitoneal administration. In the present study 4-(4'-fluoro phenyl) levulinic acid semicarbazone emerged as the most active molecule, showing broad spectrum of activity with low neurotoxicity. Unsubstituted levulinic acid semicarbazone was found to be inactive in all the screens. Conclusion: The results obtained validate the hypothesis that presence of an aryl group near the semicarbazone moiety is essential for anticonvulsant activity. The results also indicate that the hydrophilic-hydrophobic site can accommodate hydrophilic groups.

关 键 词：Substituted semicarbazones ANTICONVULSANT Levulinic acid 

分 类 号：R914[医药卫生—药物化学]