细胞松弛素A的共轭羰基在收缩抑制中的作用。

The role of the conjugated carbonyl of cytochalasin A in contractility inhibitions.

作者信息

Tanenbaum S W, Patwardhan B H, Haynes L, Flashner M

出版信息

Life Sci. 1982 May 31;30(22):1927-31. doi: 10.1016/0024-3205(82)90474-x.

Abstract

A study of the mechanism of action of cytochalasin A (CA) in relation to its structural features and to its selective inhibition of certain contractile processes has been initiated. Quantitative structure-function analyses with several CA-related cytochalasins - including synthetic 21,22-dihydro-CA (DHCA), the 22-beta mercaptoethanol CA-adduct, (CA-2ME), and the 22-dithiothreitol CA-adduct (CA-DTT) - have been carried out in a temperature sensitive gel-sol extract from Ehrlich ascites tumor cells. Each drug congener was purified to homogeneity by HPLC prior to biological testing. The undiminished inhibitory indices of DHCA and CA-2ME (ID50 congruent to 3.7 x 10(-7) M) overrules the prior circumstantial evidence accumulated for the obligatory electrophilic interaction of this drug, at its alpha-beta-unsaturated ketone region, with presumptive receptor nucleophiles.

摘要

一项关于细胞松弛素A（CA）的作用机制与其结构特征以及对某些收缩过程的选择性抑制之间关系的研究已经启动。已经在来自艾氏腹水瘤细胞的温度敏感凝胶-溶胶提取物中，对几种与CA相关的细胞松弛素进行了定量结构-功能分析，这些细胞松弛素包括合成的21,22-二氢-CA（DHCA）、22-β-巯基乙醇CA加合物（CA-2ME）和22-二硫苏糖醇CA加合物（CA-DTT）。在进行生物学测试之前，每种药物同系物都通过高效液相色谱法纯化至同质。DHCA和CA-2ME的抑制指数未降低（ID50相当于3.7×10^(-7) M），这推翻了此前积累的关于该药物在其α-β-不饱和酮区域与假定受体亲核试剂发生强制性亲电相互作用的间接证据。