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Peer-reviewed veterinary case report

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

Journal:
Bioorganic & medicinal chemistry
Year:
2013
Authors:
Hu, Laixing et al.
Affiliation:
Department of Chemistry · United States

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.

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Original publication: https://pubmed.ncbi.nlm.nih.gov/24012380/