Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, Karl-Franzens University, Universitätsplatz 1, A-8010 Graz, Austria.
Eur J Med Chem. 2012 Jan;47(1):510-9. doi: 10.1016/j.ejmech.2011.11.022. Epub 2011 Nov 18.
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 ω-(4-piperazin-1-yl)alkanoates showed high antitrypanosomal (IC(50)≤0.087μM) and antiplasmodial activity (IC(50)≤0.06μM). The most active ω-(4-methylpiperazin-1-yl)alkyl-2-azabicyclo-nonane possessed higher antiplasmodial activity (IC(50)≤0.023μM) and selectivity (S.I.=IC(50) (Cytotox.)/IC(50) (P. falciparum)=2188) than the antimalarial drug chloroquine (IC(50)=0.15μM, S.I.=1257).
将 4-甲基哌嗪基作为取代基插入双环化合物的桥头，或作为其氨基酰基和氨基烷基侧链的末端基团。将新化合物在体外针对多药耐药性恶性疟原虫 K(1)株和布氏锥虫罗得西亚株（STIB 900）进行了活性测试。将结果与以前制备的类似物和现有药物进行了比较。一些双环-octyl ω-(4-哌嗪-1-基)烷酸酯具有很高的抗锥虫（IC(50)≤0.087μM）和抗疟原虫活性（IC(50)≤0.06μM）。最活跃的 ω-(4-甲基哌嗪-1-基)烷基-2-氮杂双环-nonane 具有更高的抗疟原虫活性（IC(50)≤0.023μM）和选择性（S.I.=IC(50) (Cytotox.)/IC(50) (P. falciparum)=2188），优于抗疟药氯喹（IC(50)=0.15μM，S.I.=1257）。
