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Bioorg Med Chem. 2013 Nov 1;21(21):6732-41. doi: 10.1016/j.bmc.2013.08.006. Epub 2013 Aug 13.

Synthesis and antiprotozoal activity of dicationic 2,6-diphenylpyrazines and aza-analogues.

Author information

1
Department of Chemistry, Georgia State University, Atlanta, GA 30303-3083, USA; Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.

Abstract

Dicationic 2,6-diphenylpyrazines, aza-analogues and prodrugs were synthesized; evaluated for DNA affinity, activity against Trypanosoma brucei rhodesiense (T. b. r.) and Plasmodium falciparum (P. f.) in vitro, efficacy in T. b. r. STIB900 acute and T. b. brucei GVR35 CNS mouse models. Most diamidines gave poly(dA-dT)2 ΔTm values greater than pentamidine, IC50 values: T. b. r. (4.8-37nM) and P. f. (10-52nM). Most diamidines and prodrugs gave cures for STIB900 model (11, 19a and 24b 4/4 cures); 12 3/4 cures for GVR35 model. Metabolic stability half-life values for O-methylamidoxime prodrugs did not correlate with STIB900 results.

KEYWORDS:

2,6-Diarylpyrazines; Antimalarial agents; Antitrypanosomal agents; Diamidines; Prodrugs

PMID:
24012380
PMCID:
PMC3846175
DOI:
10.1016/j.bmc.2013.08.006
[Indexed for MEDLINE]
Free PMC Article

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