| Autor: |
Vodnala, Suman K., Lundbäck, Thomas, Sjöberg, Birger, Svensson, Richard, Rottenberg, Martin E., Hammarström, Lars G. J. |
| Zdroj: |
Antimicrobial Agents and Chemotherapy; December 2012, Vol. 57 Issue: 2 p1012-1018, 7p |
| Abstrakt: |
ABSTRACTNew drugs for the treatment of human African trypanosomiasis are urgently needed. A number of 2-aminopyrazines/2-aminopyridines were identified as promising leads following a focused screen of 5,500 compounds for Trypanosoma bruceisubsp. bruceiviability. Described compounds are trypanotoxic in the submicromolar range and show comparably low cytotoxicity on representative mammalian cell lines. Specifically, 6-([6-fluoro-3,4-dihydro-2H-1-benzopyran-4-yl)]oxy)-N-(piperidin-4-yl)pyrazin-2-amine (CBK201352) is trypanotoxic for T. bruceisubsp. brucei, T. bruceisubsp. gambiense, and T. bruceisubsp. rhodesienseand is nontoxic to mammalian cell lines, and in vitropreclinical assays predict promising pharmacokinetic parameters. Mice inoculated intraperitoneally (i.p.) with 25 mg/kg CBK201352 twice daily for 10 days, starting on the day of infection with T. bruceisubsp. brucei, show complete clearance of parasites for more than 90 days. Thus, CBK201352 and related analogs are promising leads for the development of novel treatments for human African trypanosomiasis. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
