Antimicrobial Agents and Chemotherapy 2013-02-01

In vitro and in vivo activities of 2-aminopyrazines and 2-aminopyridines in experimental models of human African trypanosomiasis.

Suman K Vodnala, Thomas Lundbäck, Birger Sjöberg, Richard Svensson, Martin E Rottenberg, Lars G J Hammarström

Index: Antimicrob. Agents Chemother. 57(2) , 1012-8, (2013)

Full Text: HTML

Abstract

New 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 brucei subsp. brucei viability. 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. brucei subsp. brucei, T. brucei subsp. gambiense, and T. brucei subsp. rhodesiense and is nontoxic to mammalian cell lines, and in vitro preclinical 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. brucei subsp. 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.

Related Compounds

Related Articles:

Determination of major sialylated N-glycans and identification of branched sialylated N-glycans that dynamically change their content during development in the mouse cerebral cortex.

2014-12-01

[Glycoconj. J. 31(9) , 671-83, (2014)]

One-pot synthesis of 2-phenylimidazo[1,2-α]pyridines from acetophenone, [Bmim]Br(3) and 2-aminopyridine under solvent-free conditions.

2012-01-01

[Molecules 17(11) , 13368-75, (2012)]

Synthesis and Characterization of a Novel Phenolic Lipid for Use as Potential Lipophilic Antioxidant and as a Prodrug of Butyric Acid.

2015-01-01

[J. Oleo Sci. 64 , 845-52, (2015)]

Aryl H-phosphonates 17: (N-aryl)phosphoramidates of pyrimidine nucleoside analogues and their synthesis, selected properties, and anti-HIV activity.

2011-10-13

[J. Med. Chem. 54 , 6482-91, (2011)]

Synthesis and characterization of binary and ternary complexes of Co(II), Ni(II), Cu(II) and Zn(II) ions based on 4-aminotoluene-3-sulfonic acid.

2013-03-15

[Spectrochim. Acta. A. Mol. Biomol. Spectrosc. 105 , 109-24, (2013)]

More Articles...