Synthesis and antiplasmodial activity of betulinic acid and ursolic acid analogues.
Synthesis and antiplasmodial activity of betulinic acid and ursolic acid analogues.
复制标题
β酸和ursolic酸类似物的合成和抗血流活性。
DOI：
10.3390/molecules171012003
复制
发表时间：
2012-10-12
期刊：
影响因子：
--
通讯作者：
Gnoatto SC
中科院分区：
文献类型：
--
作者：
Innocente AM;Silva GN;Cruz LN;Moraes MS;Nakabashi M;Sonnet P;Gosmann G;Garcia CR;Gnoatto SC
超过40%的世界人口面临感染疟疾的风险，主要影响热带和亚热带地区的贫困人口。抗疟疾药物疗法利用了植物衍生产品，如奎宁和青蒿素及其衍生物。然而，这些抗疟药物在世界范围内的使用导致了抗药性寄生虫的传播，导致疟疾发病率和死亡率增加。考虑到文献已经证明了三萜类化合物，特别是桦木酸（1）和熊果酸（2）的抗疟潜力，本研究考察了在C-3和C-28处修饰的1和2的一些新衍生物对恶性疟原虫氯喹敏感的3D 7株的抗疟活性。抗疟原虫研究采用流式细胞术和荧光分光光度法分析，使用YOYO-1、二氢乙锭和Fluo 4/AM染色。在得到的六种类似物中，化合物1c和2c显示出优异的活性（IC 50分别为220和175 nM），而1a和B显示出良好的活性（IC 50分别为4和5 μM）。对HEK 293 T细胞进行细胞毒性评价后，1a无毒性，而1c和2c显示IC 50为4 μM，选择性指数（SI）值分别为18和23。此外，呈现最佳抗疟原虫活性的化合物2c涉及钙调节途径。
More than 40% of the World population is at risk of contracting malaria, which affects primarily poor populations in tropical and subtropical areas. Antimalarial pharmacotherapy has utilised plant-derived products such as quinine and artemisinin as well as their derivatives. However, worldwide use of these antimalarials has caused the spread of resistant parasites, resulting in increased malaria morbidity and mortality. Considering that the literature has demonstrated the antimalarial potential of triterpenes, specially betulinic acid (1) and ursolic acid (2), this study investigated the antimalarial activity against P. falciparum chloroquine-sensitive 3D7 strain of some new derivatives of 1 and 2 with modifications at C-3 and C-28. The antiplasmodial study employed flow cytometry and spectrofluorimetric analyses using YOYO-1, dihydroethidium and Fluo4/AM for staining. Among the six analogues obtained, compounds 1c and 2c showed excellent activity (IC50 = 220 and 175 nM, respectively) while 1a and b demonstrated good activity (IC50 = 4 and 5 μM, respectively). After cytotoxicity evaluation against HEK293T cells, 1a was not toxic, while 1c and 2c showed IC50 of 4 μM and a selectivity index (SI) value of 18 and 23, respectively. Moreover, compound 2c, which presents the best antiplasmodial activity, is involved in the calcium-regulated pathway(s).
登录
查看更多内容
影响因子：
10.3
作者：
Beraldo, Flavlo H.;Mikoshiba, Katsuhiko;Garcia, Celia R. S.
通讯作者：
Garcia, Celia R. S.
影响因子：
7.8
作者：
Beraldo, Flavio H;Almeida, Fabiana M;da Silva, Aline M;Garcia, Celia R S
通讯作者：
Garcia, Celia R S
低钙环境中的钙信号传导：细胞内疟疾寄生虫如何解决该问题。
DOI：
10.1083/jcb.200212130
发表时间：
2003-04-14
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gazarini ML;Thomas AP;Pozzan T;Garcia CR
通讯作者：
Garcia CR
影响因子：
5.4
作者：
Liu, H
通讯作者：
Liu, H
2-Cyano-3-（4-苯基哌嗪-1-羧酰基）Quinoxaline 1,4-二氧化物衍生物的抗血统和利什甘脉活性。
DOI：
10.3390/molecules17089451
发表时间：
2012-08-07
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Barea C;Pabón A;Galiano S;Pérez-Silanes S;Gonzalez G;Deyssard C;Monge A;Deharo E;Aldana I
通讯作者：
Aldana I