Structure-activity relationship of an ozonide carboxylic acid (OZ78) against Fasciola hepatica.
Structure-activity relationship of an ozonide carboxylic acid (OZ78) against Fasciola hepatica.
复制标题
DOI：
10.1021/jm100226t
复制
发表时间：
2010-05-27
影响因子：
7.3
通讯作者：
Vennerstrom JL
中科院分区：
文献类型：
--
作者：
Zhao Q;Vargas M;Dong Y;Zhou L;Wang X;Sriraghavan K;Keiser J;Vennerstrom JL
在本文中，我们描述了臭氧化物羧酸OZ 78（1）的SAR作为我们寻找杀吸虫合成过氧化物药物开发候选者的第一部分。我们发现，相对较小的结构变化，1导致最常见的是在体内对肝片吸虫的活性损失。活性需要螺金刚烷亚结构和酸性官能团（或酯前药）。26个新化合物以100 mg/kg剂量单次口服给药F.肝感染的大鼠中，8只具有统计学显著的蠕虫负担减少，7只部分治愈，1只（酰基磺酰胺6）完全治愈，并且在杀吸虫效力方面与1只相当。本研究还表明，1的活性是过氧化物键依赖性的，这表明其杀吸虫效力取决于F.肝。
In this paper, we describe the SAR of ozonide carboxylic acid OZ78 (1) as the first part of our search for a trematocidal synthetic peroxide drug development candidate. We found that relatively small structural changes to 1 resulted most commonly in loss of activity against Fasciola hepatica in vivo. A spiroadamantane substructure and acidic functional group (or ester prodrug) were required for activity. Of twenty-six new compounds administered at single 100 mg/kg oral doses to F. hepatica-infected rats, eight had statistically significant worm burden reductions, seven were partially curative, and one (acyl sulfonamide 6) was completely curative and comparable to 1 in flukicidal efficacy. This study also showed that the activity of 1 is peroxide bond-dependent suggesting that its flukicidal efficacy depends upon hemoglobin digestion in F. hepatica.
登录
查看更多内容
影响因子：
3.6
作者：
Dong, YX;Vennerstrom, JL
通讯作者：
Vennerstrom, JL
影响因子：
5.2
作者：
Keiser, Jennifer;Shu-Hua, Xiao;Utzinger, Jurg
通讯作者：
Utzinger, Jurg
影响因子：
2.7
作者：
Padmanilayam, Maniyan;Scorneaux, Bernard;Vennerstrom, Jonathan L.
通讯作者：
Vennerstrom, Jonathan L.
影响因子：
4.9
作者：
Kaiser, Marcel;Wittlin, Sergio;Vennerstrom, Jonathan L.
通讯作者：
Vennerstrom, Jonathan L.
DOI：
10.4269/ajtmh.2008.78.388
发表时间：
2008-03-01
影响因子：
3.3
作者：
Hien, Tran Tinh;Truong, Ng Thanh;Day, Jeremy N.
通讯作者：
Day, Jeremy N.