Schleiferböck Sarah, Scheurer Christian, Ihara Masataka, Itoh Isamu, Bathurst Ian, Burrows Jeremy N, Fantauzzi Pascal, Lotharius Julie, Charman Susan A, Morizzi Julia, Shackleford David M, White Karen L, Brun Reto, Wittlin Sergio
Swiss Tropical and Public Health Institute, Basel, Switzerland ; University of Basel, Basel, Switzerland.
Drug Des Devel Ther. 2013 Nov 15;7:1377-84. doi: 10.2147/DDDT.S51298. eCollection 2013.
The objective of this work was to characterize the in vitro (Plasmodium falciparum) and in vivo (Plasmodium berghei) activity profile of the recently discovered lead compound SSJ-183. The molecule showed in vitro a fast and strong inhibitory effect on growth of all P. falciparum blood stages, with a tendency to a more pronounced stage-specific action on ring forms at low concentrations. Furthermore, the compound appeared to be equally efficacious on drug-resistant and drug-sensitive parasite strains. In vivo, SSJ-183 showed a rapid onset of action, comparable to that seen for the antimalarial drug artesunate. SSJ-183 exhibited a half-life of about 10 hours and no significant differences in absorption or exposure between noninfected and infected mice. SSJ-183 appears to be a promising new lead compound with an attractive antimalarial profile.
这项工作的目的是表征最近发现的先导化合物SSJ - 183的体外（恶性疟原虫）和体内（伯氏疟原虫）活性谱。该分子在体外对所有恶性疟原虫血液阶段的生长显示出快速而强烈的抑制作用，在低浓度下对环状体有更明显的阶段特异性作用倾向。此外，该化合物对耐药和药物敏感的寄生虫菌株似乎同样有效。在体内，SSJ - 183显示出快速起效，与抗疟药物青蒿琥酯相当。SSJ - 183的半衰期约为10小时，未感染和感染小鼠之间在吸收或暴露方面无显著差异。SSJ - 183似乎是一种有前景的新型先导化合物，具有吸引人的抗疟特性。
