苄基异喹啉化合物可抑制钙调蛋白激活环核苷酸磷酸二酯酶的能力。

Benzylisoquinoline compounds inhibit the ability of calmodulin to activate cyclic nucleotide phosphodiesterase.

作者信息

Hu Z Y, Chen S L, Hao Z G, Huang W L, Peng S X

机构信息

Division of Biochemistry, China Pharmaceutical University, Nanjing.

出版信息

Cell Signal. 1989;1(2):181-5. doi: 10.1016/0898-6568(89)90008-9.

DOI:10.1016/0898-6568(89)90008-9

PMID:2561985

Abstract

Benzylisoquinoline compounds antagonised the ability of calmodulin (CaM) to stimulate the activity of calmodulin-dependent cyclic nucleotide phosphodiesterase (CaM-PDE). This 'anti-CaM' activity was related to the hydrophobicity of the non-polar terminal region of the antagonist molecule. Antagonistic potency increased with the increase of hydrophobicity; the anti-CaM activity did not change when the polar terminus was a tertiary amine or quarternary amine. The anti-CaM potency was greater for bisbenzylisoquinoline compounds than for monobenzylisoquinoline compounds. Among the bisbenzylisoquinoline compounds anti-CaM pathway was: D3 greater than D2 berbamine greater than daurisoline greater than dauricine. Compound D3, which exhibited an IC50 value of 2.8 microM, was one of the most potent calmodulin antagonists, among benzylisoquinoline compounds, so far reported.

摘要

苄基异喹啉化合物拮抗钙调蛋白（CaM）刺激钙调蛋白依赖性环核苷酸磷酸二酯酶（CaM-PDE）活性的能力。这种“抗CaM”活性与拮抗剂分子非极性末端区域的疏水性有关。拮抗效力随疏水性增加而增强；当极性末端为叔胺或季胺时，抗CaM活性不变。双苄基异喹啉化合物的抗CaM效力大于单苄基异喹啉化合物。在双苄基异喹啉化合物中，抗CaM途径为：D3＞D2＞小檗胺＞蝙蝠葛苏林碱＞蝙蝠葛碱。化合物D3的IC50值为2.8 microM，是迄今为止报道的苄基异喹啉化合物中最有效的钙调蛋白拮抗剂之一。