2-Arylpaullones are selective antitrypanosomal agents

Jasmin Ryczak; Ma'ayan Papini; Annette Lader; Abedelmajeed Nasereddin; Dmitry Kopelyanskiy; Lutz Preu; Charles L Jaffe; Conrad Kunick

doi:10.1016/j.ejmech.2013.03.065

2-Arylpaullones are selective antitrypanosomal agents

Eur J Med Chem. 2013 Jun:64:396-400. doi: 10.1016/j.ejmech.2013.03.065. Epub 2013 Apr 10.

Authors

Jasmin Ryczak¹, Ma'ayan Papini, Annette Lader, Abedelmajeed Nasereddin, Dmitry Kopelyanskiy, Lutz Preu, Charles L Jaffe, Conrad Kunick

Affiliation

¹ Technische Universität Braunschweig, Institut für Medizinische und Pharmazeutische Chemie, Beethovenstraße 55, D-38106 Braunschweig, Germany.

PMID: 23648975
DOI: 10.1016/j.ejmech.2013.03.065

Abstract

Antileishmanial paullone-chalcone hybrid molecules display antiparasitic activity against Trypanosoma brucei rhodesiense blood stream forms, albeit with low selectivity against human THP-1 cells. In order to develop less toxic analogues, paullones with acrylamide or aryl substituents in 2-position were synthesized, of which the latter exhibited potent antiparasitic activity with excellent selectivity profiles. The most potent compound identified in this study was 9-tert-butyl-2-(4-morpholinophenyl)paullone (3i) which inhibited the parasites at submicromolar concentrations (GI50 = 510 nM) with a selectivity index of 157.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Benzazepines / chemical synthesis
Benzazepines / chemistry
Benzazepines / pharmacology*
Dose-Response Relationship, Drug
Drug Evaluation, Preclinical
Molecular Structure
Parasitic Sensitivity Tests
Structure-Activity Relationship
Trypanocidal Agents / chemical synthesis
Trypanocidal Agents / chemistry
Trypanocidal Agents / pharmacology*
Trypanosoma brucei rhodesiense / drug effects*

Substances

Benzazepines
Trypanocidal Agents
paullone