Synthesis and Antiprotozoal Activity of Dicationic 2,6-diphenylpyrazines and Aza-analogues

Overview

Journal Bioorg Med Chem

Specialties Biochemistry
Chemistry

Date 2013 Sep 10

PMID 24012380

Citations 4

Authors

Laixing Hu

Alpa Patel

Lavanya Bondada

Sihyung Yang

Michael Zhuo Wang

Manoj Munde

W David Wilson

Tanja Wenzler

Reto Brun

David W Boykin

Affiliations

Soon will be listed here.

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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