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

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.

journal_name

Bioorg Med Chem

authors

Hu L,Patel A,Bondada L,Yang S,Wang MZ,Munde M,Wilson WD,Wenzler T,Brun R,Boykin DW

doi

10.1016/j.bmc.2013.08.006

subject

Has Abstract

pub_date

2013-11-01 00:00:00

pages

6732-41

issue

21

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(13)00688-3

journal_volume

21

pub_type

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