New N-methylpiperazinyl derivatives of bicyclic antiprotozoal compounds

作者：Faist Johanna; Seebacher Werner; Saf Robert; Brun Reto; Kaiser Marcel; Weis Robert^*

来源：European Journal of Medicinal Chemistry, 2012, 47: 510-519.

DOI：10.1016/j.ejmech.2011.11.022

• 5-(4-Methylpiperazinyl)-2-azabicyclo-nonanes
• 4-(4-Methylpiperazinyl)bicyclo-octanes
• Plasmodium falciparum
• Trypanosoma brucei rhodesiense

The 4-methylpiperazinyl group was inserted as substituent at the bridgehead of bicyclic compounds or as terminal group of their aminoacyl and aminoalkyl side chains. The new compounds were tested in vitro for their activities against the multidrug-resistant K-1 strain of Plasmodium falciparum and Trypanosoma brucei rhodesiense (STIB 900). The results were compared to those of formerly prepared analogues and of drugs in use. A couple of bicyclo-octyl omega-(4-piperazin-1-yl)alkanoates showed high antitrypanosomal (IC50 %26lt;= 0.087 mu M) and antiplasmodial activity (IC50 %26lt;= 0.06 mu M). The most active omega-(4-methylpiperazin-1-yl)alky1-2-azabicyclo-nonane possessed higher antiplasmodial activity (IC50 %26lt;= 0.023 mu M) and selectivity (S.I. = IC50 (Cytotox.)/IC50 (P. falciparum) 2188) than the antimalarial drug chloroquine (IC50 = 0.15 mu M, S.I. = 1257).

• 出版日期2012-1