Bell C A, Hall J E, Kyle D E, Grogl M, Ohemeng K A, Allen M A, Tidwell R R
Department of Parasitology, School of Public Health, University of North Carolina, Chapel Hill 27599.
Antimicrob Agents Chemother. 1990 Jul;34(7):1381-6. doi: 10.1128/AAC.34.7.1381.
The antiprotozoal compound 1,5-di(4-amidinophenoxy)pentane (pentamidine) and 36 of its analogs were screened for in vitro activity against Leishmania mexicana amazonensis clone 669 C4S (MHOM/BR/73/M2269) and Plasmodium falciparum clones W2 (Indochina III/CDC) and D6 (Sierra Leone I/CDC). Pentamidine and each of the analogs tested exhibited activity in vitro against L. m. amazonensis and P. falciparum. The pentamidine analogs were more effective against the P. falciparum clones than against L. m. amazonensis. P. falciparum was extremely susceptible to these compounds, with 50% inhibitory concentrations as low as 0.03 microM. While none of the analogs exhibited marked improvement in antileishmanial activity compared with pentamidine, 12 of the pentamidine analogs showed activity approximately equal to or greater than that of the parent compound. From the promising activity exhibited by the pentamidine analogs in this in vitro study and their potential for reduced toxicity relative to the parent drug, pentamidine-related compounds hold promise as new agents for the treatment of protozoal infections.
对抗原虫化合物1,5 - 二（4 - 脒基苯氧基）戊烷（喷他脒）及其36种类似物进行了体外活性筛选，以检测其对亚马逊利什曼原虫克隆669 C4S（MHOM/BR/73/M2269）以及恶性疟原虫克隆W2（印支III/疾病预防控制中心）和D6（塞拉利昂I/疾病预防控制中心）的活性。喷他脒及所测试的每种类似物在体外均表现出对亚马逊利什曼原虫和恶性疟原虫的活性。喷他脒类似物对恶性疟原虫克隆的效果比对亚马逊利什曼原虫更好。恶性疟原虫对这些化合物极为敏感，50%抑制浓度低至0.03微摩尔。虽然与喷他脒相比，没有一种类似物在抗利什曼原虫活性方面表现出显著改善，但12种喷他脒类似物的活性约等于或高于母体化合物。鉴于喷他脒类似物在这项体外研究中展现出的有前景的活性以及它们相对于母体药物潜在的更低毒性，与喷他脒相关的化合物有望成为治疗原虫感染的新型药物。
