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

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

文献索引：Bioorg. Med. Chem. 21(21) , 6732-41, (2013)

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摘要

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. Copyright © 2013 Elsevier Ltd. All rights reserved.