Literature DB >> 24012380

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

Laixing Hu1, Alpa Patel, Lavanya Bondada, Sihyung Yang, Michael Zhuo Wang, Manoj Munde, W David Wilson, Tanja Wenzler, Reto Brun, David W Boykin.   

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.
Copyright © 2013 Elsevier Ltd. All rights reserved.

Entities:  

Keywords:  2,6-Diarylpyrazines; Antimalarial agents; Antitrypanosomal agents; Diamidines; Prodrugs

Mesh：

Substances：

Year:  2013        PMID： 24012380      PMCID： PMC3846175          DOI： 10.1016/j.bmc.2013.08.006

Source DB:  PubMed          Journal:  Bioorg Med Chem        ISSN： 0968-0896            Impact factor:   3.641


  35 in total

1.  Strong binding in the DNA minor groove by an aromatic diamidine with a shape that does not match the curvature of the groove.

Authors:  Binh Nguyen; Michael P H Lee; Donald Hamelberg; Alexandra Joubert; Christian Bailly; Reto Brun; Stephen Neidle; W David Wilson
Journal:  J Am Chem Soc       Date:  2002-11-20       Impact factor: 15.419

2.  Out-of-shape DNA minor groove binders: induced fit interactions of heterocyclic dications with the DNA minor groove.

Authors:  Yi Miao; Michael P H Lee; Gary N Parkinson; Adalgisa Batista-Parra; Mohamed A Ismail; Stephen Neidle; David W Boykin; W David Wilson
Journal:  Biochemistry       Date:  2005-11-15       Impact factor: 3.162

3.  In vitro metabolism of an orally active O-methyl amidoxime prodrug for the treatment of CNS trypanosomiasis.

Authors:  J H Ansede; R D Voyksner; M A Ismail; D W Boykin; R R Tidwell; J E Hall
Journal:  Xenobiotica       Date:  2005-03       Impact factor: 1.908

4.  Unusual dehydroxylation of antimicrobial amidoxime prodrugs by cytochrome b5 and NADH cytochrome b5 reductase.

Authors:  Janelle Y Saulter; Joseph R Kurian; Lauren A Trepanier; Richard R Tidwell; Arlene S Bridges; David W Boykin; Chad E Stephens; Mariappan Anbazhagan; James Edwin Hall
Journal:  Drug Metab Dispos       Date:  2005-08-30       Impact factor: 3.922

Review 5.  Aromatic diamidines as antiparasitic agents.

Authors:  M N C Soeiro; E M De Souza; C E Stephens; D W Boykin
Journal:  Expert Opin Investig Drugs       Date:  2005-08       Impact factor: 6.206

Review 6.  Dications that target the DNA minor groove: compound design and preparation, DNA interactions, cellular distribution and biological activity.

Authors:  W David Wilson; Binh Nguyen; Farial A Tanious; Amanda Mathis; James Edwin Hall; Chad E Stephens; David W Boykin
Journal:  Curr Med Chem Anticancer Agents       Date:  2005-07

7.  Synthesis and antiprotozoal activity of aza-analogues of furamidine.

Authors:  Mohamed A Ismail; Reto Brun; Judy D Easterbrook; Farial A Tanious; W David Wilson; David W Boykin
Journal:  J Med Chem       Date:  2003-10-23       Impact factor: 7.446

Review 8.  Diamidines as antitrypanosomal, antileishmanial and antimalarial agents.

Authors:  Karl Werbovetz
Journal:  Curr Opin Investig Drugs       Date:  2006-02

9.  Characterization of a novel DNA minor-groove complex.

Authors:  Binh Nguyen; Donald Hamelberg; Christian Bailly; Pierre Colson; Jaroslav Stanek; Reto Brun; Stephen Neidle; W David Wilson
Journal:  Biophys J       Date:  2004-02       Impact factor: 4.033

10.  O-alkoxyamidine prodrugs of furamidine: in vitro transport and microsomal metabolism as indicators of in vivo efficacy in a mouse model of Trypanosoma brucei rhodesiense infection.

Authors:  John H Ansede; Mariappan Anbazhagan; Reto Brun; Judy D Easterbrook; James Edwin Hall; David W Boykin
Journal:  J Med Chem       Date:  2004-08-12       Impact factor: 7.446
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  4 in total

1.  In vitro and in vivo evaluation of 28DAP010, a novel diamidine for treatment of second-stage African sleeping sickness.

Authors:  Tanja Wenzler; Sihyung Yang; Donald A Patrick; Olivier Braissant; Mohamed A Ismail; Richard R Tidwell; David W Boykin; Michael Zhuo Wang; Reto Brun
Journal:  Antimicrob Agents Chemother       Date:  2014-05-27       Impact factor: 5.191

2.  Bis-benzimidazole hits against Naegleria fowleri discovered with new high-throughput screens.

Authors:  Christopher A Rice; Beatrice L Colon; Mehmet Alp; Hakan Göker; David W Boykin; Dennis E Kyle
Journal:  Antimicrob Agents Chemother       Date:  2015-01-20       Impact factor: 5.191

3.  Phenotypic Screening In Vitro of Novel Aromatic Amidines against Trypanosoma cruzi.

Authors:  M R Simões-Silva; A S G Nefertiti; J S De Araújo; M M Batista; P B Da Silva; M T Bahia; R S Menna-Barreto; B P Pavão; J Green; A A Farahat; A Kumar; D W Boykin; M N C Soeiro
Journal:  Antimicrob Agents Chemother       Date:  2016-07-22       Impact factor: 5.191

4.  Molecular characterization of myotonic dystrophy fibroblast cell lines for use in small molecule screening.

Authors:  Jana R Jenquin; Alana P O'Brien; Kiril Poukalov; Yidan Lu; Jesus A Frias; Hannah K Shorrock; Jared I Richardson; Hormoz Mazdiyasni; Hongfen Yang; Robert W Huigens; David Boykin; Laura P W Ranum; John Douglas Cleary; Eric T Wang; J Andrew Berglund
Journal:  iScience       Date:  2022-04-04
  4 in total

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