Loiseau P M, Wolf J G, Gayral P
Biologie et Contrôle des Organismes Parasites, Université Paris-Sud, Châtenay-Malabry, France.
Trop Med Parasitol. 1993 Mar;44(1):32-6.
The spiroarsoranes are a series of pentavalent arsenicals having interesting trypanocidal properties. They are less toxic than trivalent arsenicals but their activity appear at higher doses and concentrations. The structure-activity relationships study from the first series led to a new generation of spiroarsoranes which has been synthesized and evaluated in vitro and in vivo against Trypanosoma brucei brucei bloodstream forms. Among 40 compounds, 5 were active in vitro at concentrations less than 10 mumol/l and 7 were active in vivo. The most interesting compound of this series (compound I e 2) showed an in vitro activity at 125 mumol/l after 24 hours incubation time and in vivo all the mice were cured after a subcutaneous treatment at 600 mumol/kg in one single dose. The spiranization and the substitution of para-arsanilic acid allowed to obtain a better mean survival time at 300 mumol/kg comparatively to para-arsanilic acid itself used as reference compound. Nevertheless, this second generation of compounds was less active than the selected compound of the first series which was efficient at 150 mumol/kg in subcutaneously one single dose.
螺砷杂环烷是一系列具有有趣杀锥虫特性的五价砷化合物。它们的毒性低于三价砷化合物，但其活性出现在更高的剂量和浓度下。对第一代化合物的构效关系研究催生了新一代螺砷杂环烷，已对其进行体外和体内合成及对布氏布氏锥虫血流型的评估。在40种化合物中，5种在浓度低于10 μmol/l时具有体外活性，7种具有体内活性。该系列中最有趣的化合物（化合物I e 2）在孵育24小时后，125 μmol/l时具有体外活性，体内实验中，所有小鼠在以600 μmol/kg单剂量皮下给药后均被治愈。与用作参考化合物的对氨基苯胂酸相比，螺化和对氨基苯胂酸的取代使得在300 μmol/kg时能获得更好的平均存活时间。然而，第二代化合物的活性低于第一代中选定的化合物，第一代选定化合物在150 μmol/kg皮下单剂量给药时有效。
