Synthesis of 4-aryl substituted semicarbazones of some terpenes as novel anticonvulsants.
OBJECTIVE
A series of 4-aryl substituted semicarbazones of citral and R- (-) carvone were designed and synthesized to meet the structural requirements essential for anticonvulsant activity.


METHODS
TLC evaluated purity of synthesized compounds and their structure confirmed by infrared spectroscopy, proton magnetic resonance spectroscopy and by nitrogen estimation. All the compounds were evaluated for anticonvulsant activity by maximal electroshock (MES) and subcutaneous metrazol (ScMet) induced seizure methods and minimal motor impairment was determined by rotorod test.


RESULTS
All the synthesized compounds exhibited significant protection after intraperitoneal (i.p.) administration in MES. Seventy two percent of the compounds exhibited protection in ScMet test. Some of them also showed good activity after oral administration. The results showed that anticonvulsants with cyclic and acyclic terpenoid moiety retain activity in MES as well as ScMet test. The p-fluoro aryl substituted semicarbazones emerged as the most active analogue in both cyclic and acyclic terpenes.


CONCLUSIONS
Semicarbazones with terpenoid as the lipophilic moiety resulted in compounds with broad spectrum of anticonvulsant activity and therefore, they may be utilized for the future development of novel anticonvulsants with broad spectrum of anticonvulsant activity. The results also validated pharmacophore model with four binding sites essential for anticonvulsant activity.
Aggarwal
Navneet
N
Department of Pharmaceutical Chemistry, Hindu College of Pharmacy, Sonepat, Haryana, India.
Mishra
Pradeep
P
D000080462:Acyclic Monoterpenes; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D001665:Binding Sites; D000081005:Cyclohexane Monoterpenes; D015195:Drug Design; D008297:Male; D051379:Mice; D039821:Monoterpenes / Q000138:chemical synthesis* / Q000494:pharmacology; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D012664:Semicarbazones / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D013729:Terpenes / Q000138:chemical synthesis* / Q000494:pharmacology
D000080462:Acyclic Monoterpenes; D000927:Anticonvulsants; D000081005:Cyclohexane Monoterpenes; D039821:Monoterpenes; D012664:Semicarbazones; D013729:Terpenes; C006923:carvone; C007076:citral