O-alkoxyamidine prodrugs of furamidine:: In vitro transport and microsomal metabolism as indicators of in vivo efficacy in a mouse model of Trypanosoma brucei rhodesiense infection
O-alkoxyamidine prodrugs of furamidine:: In vitro transport and microsomal metabolism as indicators of in vivo efficacy in a mouse model of Trypanosoma brucei rhodesiense infection
复制标题
DOI：
10.1021/jm030604o
复制
发表时间：
2004-08-12
影响因子：
7.3
通讯作者：
Boykin, DW
中科院分区：
文献类型：
--
作者：
Ansede, JH;Anbazhagan, M;Boykin, DW
合成了前药2，5-双[4-甲氧基脒基苯基]呋喃的五种O-烷氧基脒类似物，并通过口服给药在STIB 900小鼠模型中评价其抗布氏锥虫罗得西亚的作用。观察到的这些前药的体内活性表明，具有O-甲氧基脒或O-乙氧基脒基团的化合物有效地治愈了所有锥虫感染的小鼠，而具有较大侧链的前药不能完全治愈小鼠。使用跨Caco-2细胞单层的渗透性和微粒体代谢来鉴定前药功效的潜在机制。
Five O-alkoxyamidine analogues of the prodrug 2,5-bis[4-methoxyamidinophenyl]furan were synthesized and evaluated against Trypanosoma brucei rhodesiense in the STIB900 mouse model by oral administration. The observed in vivo activity of these prodrugs demonstrates that compounds with an O-methoxyamidine or O-ethoxyamidine group effectively cured all trypanosome-infected mice, whereas prodrugs with larger side-chains did not completely cure the mice. Permeability across Caco-2 cell monolayers and microsomal metabolism were used to identify the underlying mechanisms of prodrug efficacy.