Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 21, Issue 21, Pages 6337-6348Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2013.08.055
Keywords
Lapachol; beta-Lapachone; Quinone; Chagas disease; Trypomastigote; Click chemistry; Electrochemical parameters
Funding
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [14/2012, 480719/2012-8]
- FAPEMIG [Q-04166-10]
- PRONEM-FACEPE [1232.1.06/10]
- CENAPESQ-UFRPE
- PRONEX/FAPEAL/CNPq
- CAPES
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In our continued search for novel trypanocidal compounds, twenty-six derivatives of para-and orthonaphthoquinones coupled to 1,2,3-triazoles were synthesized. These compounds were evaluated against the infective bloodstream form of Trypanosoma cruzi, the etiological agent of Chagas disease. Compounds 17-24, 28-30 and 36-38 are described herein for the first time. Three of these novel compounds (28-30) were found to be more potent than the standard drug benznidazole, with IC50/24 h values between 6.8 and 80.8 mu M. Analysis of the toxicity to heart muscle cells led to LC50/24 h of <125, 63.1 and 281.6 mu M for 28, 29 and 30, respectively. Displaying a selectivity index of 34.3, compound 30 will be further evaluated in vivo. The electrochemical properties of selected compounds were evaluated in an attempt to find correlations with trypanocidal activity, and it was observed that more electrophilic quinones were generally more potent. (C) 2013 Elsevier Ltd. All rights reserved.
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