Donkor I O, Assefa H, Rattendi D, Lane S, Vargas M, Goldberg B, Bacchi C
Room 327E, Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis Johnson Building, 847 Monroe Avenue, Memphis, TN 38163, USA.
Eur J Med Chem. 2001 Jun;36(6):531-8. doi: 10.1016/s0223-5234(01)01250-8.
Eight dicationic compounds related to pentamidine were studied for trypanocidal activity in seven trypanosome isolates. In vitro studies revealed that diamidines are more potent than diimidazolines. For example, 2 (a diamidine) and 4 (a diimidazoline) inhibited the growth of KETRI 243 with IC50 values of 2.3 and 900 nM, respectively. Introduction of polar groups into the linker decreased the effectiveness of the compounds against drug-resistant trypanosomes. In compounds with a 2-butene linker between the cationic groups, trans-isomers were more potent than cis-isomers. The cis- and trans-buteneamidines cured infection caused by Trypanosoma brucei brucei (EATRO Lab 110) and protected mice against infection by Trypanosoma brucei rhodesiense isolates, some of which are resistant to diamidines and melarsoprol.
研究了八种与喷他脒相关的二价阳离子化合物对七种锥虫分离株的杀锥虫活性。体外研究表明，二脒比二咪唑啉更具活性。例如，2（一种二脒）和4（一种二咪唑啉）抑制KETRI 243生长的IC50值分别为2.3 nM和900 nM。在连接基中引入极性基团会降低化合物对耐药锥虫的有效性。在阳离子基团之间具有2-丁烯连接基的化合物中，反式异构体比顺式异构体更具活性。顺式和反式丁烯脒治愈了布氏布氏锥虫（EATRO实验室110）引起的感染，并保护小鼠免受罗德西亚布氏锥虫分离株的感染，其中一些分离株对二脒和美拉胂醇耐药。
