title: Synthesis and anticonvulsant activity of novel purine derivatives.
abstract: A series of new purines containing triazole and other heterocycle substituents was synthesized and evaluated for their preliminary anticonvulsant activity and neurotoxicity by using the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) and rotarod neurotoxicity (TOX) tests. Among the compounds studied, 9-decyl-6-(1H-1,2,4-triazol-1-yl)-9H-purine (5e) was the most potent compound, with a median effective dose of 23.4 mg/kg and a high protective index of more than 25.6 after intraperitoneal administration in mice. Compound 5e showed significant oral activity against MES-induced seizures in mice, with an ED50 of 39.4 mg/kg and a PI above 31.6. These results demonstrate that compound 5e possesses better anticonvulsant activity and is safer than the commercially available drugs carbamazepine and valproate in MES, scPTZ and TOX models.
authors: College of Pharmacy, Yanbian University, No. 977, Park Road, Yanji, Jilin, 133002, China.
authors: Shi-Ben
authors: SB
authors: Wang
authors: Department of Pharmacology, Ischemic/Hypoxic Disease Institute, Seoul National University, College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, Republic of Korea.
authors: Peng
authors: P
authors: Jin
authors: School of Pharmaceutical Sciences, Xiamen University, Xiang'an South Road, Xiamen, Fujian, 361102, China. Electronic address: fnlee5@xmu.edu.cn.
authors: Fu-Nan
authors: FN
authors: Li
authors: College of Pharmacy, Yanbian University, No. 977, Park Road, Yanji, Jilin, 133002, China. Electronic address: zsquan@ybu.edu.cn.
authors: Zhe-Shan
authors: ZS
authors: Quan
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D004195:Disease Models, Animal; D004597:Electroshock; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010433:Pentylenetetrazole / Q000008:administration & dosage; D011687:Purines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D012640:Seizures / Q000188:drug therapy*
chemical_list: D000927:Anticonvulsants; D011687:Purines; C030985:purine; D010433:Pentylenetetrazole
keywords: Maximal electroshock; Neurotoxicity; Pentylenetetrazole; Purine; Synthesis; Triazole