Mannich bases of scutellarein as thrombin-inhibitors: Design, synthesis, biological activity and solubility
Mannich bases of scutellarein as thrombin-inhibitors: Design, synthesis, biological activity and solubility
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灯盏乙素曼尼希碱作为凝血酶抑制剂：设计、合成、生物活性和溶解度
DOI：
10.1016/j.bmc.2012.10.015
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发表时间：
2012-12-15
影响因子：
3.5
通讯作者：
Duan, Jian-Ao
中科院分区：
文献类型：
--
作者：
Li, Nian-Guang;Song, Shu-Lin;Duan, Jian-Ao
以黄芩素（2）为原料，分别与脂肪胺、脂环胺和甲醛进行Mannich反应，合成了两个系列的8-氨甲基化衍生物。通过测定凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、凝血酶时间（TT）和纤维蛋白原（FIB），对化合物的凝血酶抑制活性进行了测定。采用3-（4，5）-二甲基噻唑-3，5-二苯基四氮唑溴化物（MTT）法测定2，2-二苯基-1-（2，4，6-三硝基苯基）-1，1-二苯-2-苦肼基（DPPH）的抗氧化活性，并采用紫外分光光度法测定其溶解性。结果表明，吗啉基氨基亚甲基取代衍生物（3d）的抗凝血活性、水溶性和抗氧化活性均优于野黄芩素（2），可作为缺血性脑血管病的治疗药物进一步开发。(C)2012爱思唯尔有限公司保留所有权利。
Two series of 8-aminomethylated derivatives were prepared by Mannich reaction of scutellarein (2) with appropriate aliphatic amines, alicyclic amines and formaldehyde. All the compounds were tested for their thrombin inhibition activity through the analyzation of prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and fibrinogen (FIB). The antioxidant activities of these target products were assessed by 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH) assay using 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay method and the solubility were assessed by ultraviolet (UV). The results showed that morpholinyl aminomethylene substituent derivative (3d) demonstrated stronger anticoagulant activity, better water solubility and good antioxidant activity compared with scutellarein (2), which warrants further development as a agent for ischemic cerebrovascular disease treatment. (C) 2012 Elsevier Ltd. All rights reserved.