Seebacher Werner, Brun Reto, Kaiser Marcel, Saf Robert, Weis Robert
Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, Karl-Franzens-University, Universitätsplatz 1, A-8010 Graz, Austria.
Eur J Med Chem. 2005 Sep;40(9):888-96. doi: 10.1016/j.ejmech.2005.03.018.
Several new 4-amino-6,7-diphenylbicyclo[2.2.2]octane derivatives, methylthiosemicarbazones of bicyclo[2.2.2]octan-2-ones and esters of bicyclo[2.2.2]octan-2-ols were prepared. Their antitrypanosomal activities against Trypanosoma brucei rhodesiense (STIB 900) and their antiplasmodial activity against the K1 strain of Plasmodium falciparum (resistant to chloroquine and pyrimethamine) were investigated using microplate assays. In addition to that, the cytotoxicity of the new compounds was determined using L-6 cells. The methylthiosemicarbazones show moderate antiprotozoal activities whereas some of the esters of piperonylic acid, homopiperonylic acid and 2-naphtoic acid exhibit remarkable antitrypanosomal and antiplasmodial activity.
制备了几种新型的4-氨基-6,7-二苯基双环[2.2.2]辛烷衍生物、双环[2.2.2]辛烷-2-酮的甲硫基氨基脲以及双环[2.2.2]辛烷-2-醇的酯。使用微孔板分析法研究了它们对布氏罗得西亚锥虫（STIB 900）的抗锥虫活性以及对恶性疟原虫K1株（对氯喹和乙胺嘧啶耐药）的抗疟活性。此外，使用L-6细胞测定了新化合物的细胞毒性。甲硫基氨基脲显示出中等的抗原虫活性，而胡椒酸、高胡椒酸和2-萘甲酸的一些酯表现出显著的抗锥虫和抗疟活性。
