钙调素拮抗剂──双苄基异喹啉类化合物结构与活性关系的研究  

Calmodnlin Antagonist——Study on Structure-activity Relationship of Bis-benzylisoquinoline Compounds

作　　者：陈少林[1] 胡卓逸[1] 郝志奇 蔡惠明[2] 黄文龙[2] 

机构地区：[1]中国药科大学生物化学研究室 [2]中国药科大学药物化学研究室

出　　处：《生物化学杂志》1990年第5期413-416,共4页

基　　金：国家自然科学基金资助课题~~

摘　　要：双苄基异喹啉类化合物拮抗钙调素(CaM),抑制CaM激活的环核苷酸磷酸二酯酶(PDE),研究表明:蝙蝠葛碱和小檗胺分子中12位羟墓被芳香基团酯化或醚化时,芳香基团的电子云分布状态变化能增加或降低分子的拮抗活性;取代基中的次甲基数增加可以增强分子的拮抗活性。分子非极性端引入含氮基团,化合物的拮抗活性较低。测试的化合物中,E_6D_(12)和D_(14)的拮抗CaM活性较强,IC_(50)分别为0.58μmol/L0.58μmol/L和0.53μmol/L。实验结果表明,分子的拮抗活性与分子非极性端的疏水性、电子云分布状态以及分子空间结构等多种结构性质相关。Bis-benzylisoquinoline compounds antagonized calmoduIin(CaM) to inhibit the activity of CaM-dependent cyclic nucleotide phosphodiesterase(PDE) . The results showed that as the 12-hydroxyl in dauricine or berbamine was esterified or e-therized by aromatic groups the changes occured in electron cloud distributions of the aromatic groups led to enhance or reduce the molecular anti-CaM activity; extending the alkyl chains of the substituents could enhance the molecular anti-CaM activity; the anti-CaM ability was diminished by introducing nicotinoyl groups at nonpolar terminus of the compounds; among the tested compounds D14,D12 and E6 showed stronger inhibitory effect on CaM, with IC50 of 0.53μmol/L 0.58μmal/L and 0.58μmol/L respectively. The results suggested that the anti-CaM ability of the compounds was relevant to multiple structural conditions such as hydrophobicity of the nonpolar terminus changes in electron cloud distribution and space structure.

关 键 词：钙调素 钙调素拮抗剂 双苄基异喹啉 

分 类 号：R962[医药卫生—药理学]