Structural aspects of flavonoids as trypsin inhibitors
Structural aspects of flavonoids as trypsin inhibitors
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DOI：
10.1016/j.ejmech.2003.12.003
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发表时间：
2004-03-01
影响因子：
6.7
通讯作者：
Sturdík, E
中科院分区：
文献类型：
--
作者：
Maliar, T;Jedinák, A;Sturdík, E
在寻找新的蛋白酶抑制剂的过程中，我们主要关注多酚类化合物的筛选和计算机辅助药物设计（CADD）研究。本文报道了胰蛋白酶抑制剂黄酮醇和黄酮类化合物的CADD筛选结果。5，7-二羟基类黄酮是一种很有前景的胰蛋白酶/胰蛋白酶样酶抑制剂。黄烷酮和异黄酮是不太有效的胰蛋白酶抑制剂，因为失去了最佳的几何结构，导致氢键相互作用。观察到四种不同的相互作用模式，黄酮类化合物通过形成两个（芹菜素）或至少一个氢键和其他显著的静电相互作用稳定在P-胰蛋白酶的S'区。槲皮素、杨梅素和桑色素已被证明是最好的胰蛋白酶抑制剂。通常，具有适当位置的羟基和平面构象的类黄酮是能够取代成功抑制剂的胍基苯甲酰基部分的结构单元。黄酮类化合物的生理特性揭示了新型胰蛋白酶抑制剂作为抗胰腺炎、抗癌和抗炎药物的生物技术来源。(C)2004年，Elsevier SAS。All rights reserved.
In the search for new proteinase inhibitors we have focused on the screening and Computer Assisted Drug Design (CADD) studies of polyphenolic compounds. In this paper we report CADD of flavonoles and flavones as trypsin inhibitors concomitant by the screening results. 5,7-Dihydroxy flavonoid have been found to be a perspective trypsin/trypsin-like-enzyme inhibitor. Flavanones and isoflavones are less effective trypsin inhibitors due to a lost of the optimal geometry leading to hydrogen bond interactions. Four different interaction modes were observed, flavonoids are stabilised in S' region of P-trypsin by formation of two (apigenin) or at least one hydrogen bond and other significant electrostatic interactions. Quercetin, myricetin and morin have shown to be the best trypsin inhibitors tested. In general, flavonoids, with suitably located hydroxy groups and planar conformation are the building blocks able to replace guanidinobenzoyl part of successful inhibitors. Physiological nature of flavonoids reveals biotechnological source of new trypsin inhibitors as antipancreatitis, anticancer and anti-inflammation drugs. (C) 2004 Elsevier SAS. All rights reserved.