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

نویسندگان

  • Laixing Hu
  • Alpa Patel
  • Lavanya Bondada
  • Sihyung Yang
  • Michael Zhuo Wang
  • Manoj Munde
  • W David Wilson
  • Tanja Wenzler
  • Reto Brun
  • David W Boykin
چکیده

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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عنوان ژورنال:
  • Bioorganic & medicinal chemistry

دوره 21 21  شماره 

صفحات  -

تاریخ انتشار 2013