Effect of natural and synthetic benzyl benzoates on calmodulin
Effect of natural and synthetic benzyl benzoates on calmodulin
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DOI：
10.1016/j.phytochem.2007.02.026
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发表时间：
2007-04-01
期刊：
影响因子：
3.8
通讯作者：
Mata, Rachel
中科院分区：
文献类型：
--
作者：
Rivero-Cruz, Blanca;Rivero-Cruz, Isabel;Mata, Rachel
本调查描述了从Brickellia veronicifolia痉挛苯甲酸苄酯1-9钙调素的作用，使用功能在体外酶测定。牛脑PDE 1用作监测酶。系统CaM-PDE 1的最活跃的天然抑制剂是苯甲酸苄酯3-5，其以浓度依赖性方式抑制PDE 1的活性。此外，制备并测定了化合物4的三个系列的类似物，化合物10a-32a。第一系列的苯甲酸苄酯，即10 a-24 a，在环B上没有取代基，但在环A上具有不同数量和位置的羟基或甲氧基。另一方面，第二基团（25- 32 a）具有与化合物4上相同的A环，但在环B中具有不同的取代基。活性最高的化合物是14 a、15 a和30 a。这些化合物的效力是氯丙嗪（一种众所周知的钙调素抑制剂）的2至6倍。苯甲酸苄酯14 a和15 a分别在环A的C-2/C-4和C-3/C-4处具有甲氧基;而30 a除了在环A的C-2/C-6处的甲氧基之外，还在环B的C-3'处具有苯甲酰氧基部分。动力学研究表明，化合物3、4、14 a、15 a和30 a表现为竞争性CaM拮抗剂。(c)2007爱思唯尔有限公司保留所有权利。
The present investigation describes the effect of the spasmolytic benzylbenzoates 1-9 from Brickellia veronicifolia on CaM using a functional in vitro enzymatic assay. Bovine brain PDE1 was used as a monitoring enzyme. The most active natural inhibitors of the system CaM-PDE1 were benzyl benzoates 3-5, which inhibited the activity of PDE1 in a concentration-dependent manner. In addition, three series of analogs of compound 4, compounds 10a-32a, were prepared and assayed. The benzyl benzoates from the first series, namely 10a-24a, possess no substituents on ring B but different number and position of hydroxyl or methoxy groups in ring A. The second group (25-32a), on the other hand, possesses an A ring identical to that on compound 4, but different substituents in Ring B. The most active compounds were 14a, 15a and 30a. These compounds were two to six times more potent than chlorpromazine, a well known CaM inhibitor. Benzyl benzoates 14a and 15a have methoxyl groups at C-2/C-4 and C-3/C-4 in ring A, respectively; while 30a, in addition to the methoxyl groups at C-2/C-6 of ring A, hold a benzoyloxy moiety at C-3' of ring B. Kinetic studies revealed that compounds 3, 4, 14a, 15a and 30a behave as competitive CaM antagonists. (c) 2007 Elsevier Ltd. All rights reserved.