张奕华 1HUSSAINIIsaM 2SHENTsungY3
作者信息
- 1. 中国药科大学新药研究中心,南京,210009
- 2. 美国维吉尼亚大学病理系
- 3. 美国维吉尼亚大学化学系
- 折叠
摘要
Abstract
AIM:To investigate a new type of dual acting anti-inflammatory agents. METHOD:A group of novel dithiolane derivatives and their analogs were synthesized. The effects of several dithiolane compounds and a highly potent and selective PAF-receptor antagonist,L659,989 on PAF-receptor binding,IFN-γ and LPS-induced NO production and steady state iNOS mRNA expression were determined. RESULT:Among forty new compounds(1～40) synthesized,nineteen compounds were found to inhibit the production of NO at different levels. The three most active compounds(2,19,20) appeared to decrease iNOS mRNA expression. The order of relative potency of the inhibition of NO production from high to low is 19,20,2 ,L659,989, while the potency for blocking PAF-receptor from high to low is L659,989,20,2,19. The PAF antagonist,L659,989 showed no effect on NO production and iNOS mRNA expression. Among the dithiolane derivatives tested,there is also no simple correlation between their PAF-receptor antagonism and iNOS inhibitory activities. CONCLUSION:Dithiolane derivatives and their analogs are a new synthetic chemical class of iNOS expression regulators,some of which have dual biological functions:inhibiting iNOS induction and blocking PAF-receptor. More potent compounds with such dual actions may be useful synthetic therapeutic agents under various conditions such as septic shock and inflammatory disorders where the reduction of both NO production and PAF activity would be desirable.关键词
NO/iNOS抑制剂/PAF受体拮抗剂/双重作用/合成/活性吡啶磺酰脲类化合物的合成及其利尿和降压活性Key words
NO/PAF/iNOS inhibitors/PAF-receptor antagonists/Dual-acting/Synthesis/Activity分类
医药卫生
