Loiseau P M, Jaffe J J, Craciunescu D G
Faculté de Pharmacie, Université de Paris-Sud, Châtenay-Malabry, France.
Int J Parasitol. 1998 Aug;28(8):1279-82. doi: 10.1016/s0020-7519(98)00072-1.
New organometallic complexes having protozoocidal properties were evaluated for their in vitro antifilarial activity using two models: infective larvae of Molinema dessetae and adult females of Brugia pahangi. The compound most active on the M. dessetae model was Ir(I)-COD-pentamidine tetraphenylborate with an EC50 = 6 +/- 1 microM after 7-day-incubation. In the 2-aminobenzothiazole series, Ruthenium was more potent than Iridium for antifilarial activity. A dithiocarbamate function significantly enhanced the antifilarial activity. The compounds derived from benzimidazole were inactive whatever the metal (Iridium or Rhodium). The other compounds exhibited EC50 ranging from 10 to 31 microM. On adult female Brugia pahangi in vitro, Pt-DDH-N-acetylleucine, Pt-diminazene and Pd-Cl4-piperazine at 20 microM began to kill both microfilariae and the developing embryos within the mothers on day 2. The compounds, except for Pd-Cl4-piperazine, killed the adults after 5 days. Rh-Cl-2-chloropyridine caused obvious slowing of the adults from day 3 onward but did not affect the viability of adults, microfilariae or developing embryos. In vivo antifilarial investigations are necessary to appreciate the real advantage of heavy metal complexes in the experimental treatment of filariasis.
德氏莫林线虫的感染性幼虫和彭亨布鲁线虫的成年雌虫。在德氏莫林线虫模型上活性最高的化合物是Ir(I)-COD-喷他脒四苯基硼酸盐，孵育7天后的EC50 = 6±1微摩尔。在2-氨基苯并噻唑系列中，钌在抗丝虫活性方面比铱更有效。二硫代氨基甲酸盐官能团显著增强了抗丝虫活性。无论金属（铱或铑）如何，源自苯并咪唑的化合物均无活性。其他化合物的EC50范围为10至31微摩尔。在体外对成年彭亨布鲁线虫雌虫进行实验时，20微摩尔的Pt-DDH-N-乙酰亮氨酸、Pt-地美硝唑和Pd-Cl4-哌嗪在第2天开始杀死微丝蚴和母体内发育中的胚胎。除Pd-Cl4-哌嗪外，这些化合物在5天后杀死了成虫。Rh-Cl-2-氯吡啶从第3天起使成虫明显生长缓慢，但不影响成虫、微丝蚴或发育中胚胎的活力。有必要进行体内抗丝虫研究，以评估重金属配合物在丝虫病实验治疗中的实际优势。
