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J Med Chem. 2010 Jan 14;53(1):254-72. doi: 10.1021/jm901178d.

Synthesis and antiprotozoal activity of cationic 1,4-diphenyl-1H-1,2,3-triazoles.

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1
Department of Pathology and Laboratory Medicine, School of Medicine, The University of North Carolina, Chapel Hill, North Carolina 27599-7525, USA.

Erratum in

  • J Med Chem. 2011 Jun 23;54(12):4281.

Abstract

Novel dicationic triazoles 1-60 were synthesized by the Pinner method from the corresponding dinitriles, prepared via the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC). The type and the placement of cationic moieties as well as the nature of aromatic substituents influenced in vitro antiprotozoal activities of compounds 1-60 against Trypanosoma brucei rhodesiense, Plasmodium falciparum, and Leishmania donovani and their cytotoxicity for mammalian cells. Eight congeners displayed antitrypanosomal IC(50) values below 10 nM. Thirty-nine dications were more potent against P. falciparum than pentamidine (IC(50) = 58 nM), and eight analogues were more active than artemisinin (IC(50) = 6 nM). Diimidazoline 60 exhibited antiplasmodial IC(50) value of 0.6 nM. Seven congeners administered at 4 x 5 mg/kg by the intraperitoneal route cured at least three out of four animals in the acute mouse model of African trypanosomiasis. At 4 x 1 mg/kg, diamidine 46 displayed better antitrypanosomal efficacy than melarsoprol, curing all infected mice.

PMID:
19928900
PMCID:
PMC3113660
DOI:
10.1021/jm901178d
[Indexed for MEDLINE]
Free PMC Article

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