Synthesis and anticonvulsant activity evaluation of 3-alkoxy-4-[4- [hexyloxy/heptyloxy]phenyl]-4H-1,2,4 -triazole

A series of 3-alkoxy-4-[4-[hexyloxy/heptyloxy] phenyl]-4H-1,2,4-triazole was synthesized. The anticonvulsant effect and neurotoxicity of the compounds were calculated with maximal electroshock [MES] test and rotarod tests with intraperitoneally injected mice. Among the synthesized compounds, compound 3-heptyloxy-4-[4-[hexyloxy] phenyl]-4H-1,2,4-triazole [5f] was the most active one and also had the lowest toxicity. In the anti-MES potency test, it showed median effective dose [ED[50]] of 37.3 mg/Kg, median toxicity dose [TD[50]] of 422.5 mg/Kg, and the protective index [PI] of 11.3 which is much greater than the reference drug carbamazepine with PI value of 6.4. As well as demonstrating the anti-MES efficacy of compound 5f, its potency against seizures induced by pentylenetetrazole, 3-mercaptopropionic acid, and bicuculline were also established, with the results suggesting that GABA-mediated mechanisms might be involved in its anticonvulsant activity, such as enhancing of GABAergic neurotransmission or activity, activate GAD or inhibit GABA-T, and GABA[A]-mediated mechanisms

The differential expression profile of polycystic ovary syndrome associated genes / 北京大学学报(医学版)

Objective:To explore the gene differential expression pattern of polycystic ovary syn-drome.Methods:We carried out microarray analysis to define the gene networks by the PCOS granulosacells in order to identify differentially expressed genes in PCOS patients.These granulosa cells of fivePCOS cases and five control cases which were derived during oocyte retrieval from women undergoingIVF.Results:As compared with control human ovarian granulosa cells,46 genes were screened out,25genes were up-regulated,and 21genes were down-regulated in PCOS.These differentially expressedgenes were involved in various biologic functions,such as regulation of fatty acid metabolism,cell-cellsignal transduction,immune and inflammatory response,reflecting the complexity of clinical manifesta-tions of PCOS.Conclusion:Microarray analysis technology is an effective mothod to identify novel PCOSassociated candidate genes.