Trypanosoma cruzi: Activities of lapachol and ?- and ?-lapachone derivatives against epimastigote and trypomastigote forms

Salas C.; Tapia, R.A.; Ciudad, K; Armstrong, V; Orellana M.; Kemmerling U.; Ferreira J.; Maya J.D.; Morello A.

Keywords: oxidation, phenyl, oxygen, reduction, animals, synthesis, cell, structure, stress, trypanosoma, mechanism, cytotoxicity, alpha, beta, efficacy, quinone, viability, substitution, consumption, agents, vitro, methyl, nifurtimox, naphthoquinones, agent, radical, respiration, benznidazole, drug, molecular, article, hydroxy, trypomastigote, cruzi, concentration, potency, group, controlled, oxidative, naphthoquinone, study, 4, 3, response, derivative, lapachol, Reaction, in, nonhuman, 2, (1, 50, Free, (3, unclassified, dimethyl, 5,6, dihydro, 1,4, lapachone, antitrypanosomal, Trypanocidal, Oxidation-Reduction, Functional, 3,4, dione, 2h, 2,3, epimastigote, Stereoisomerism, IC, 5,10, naphtho[2,3, b]pyran, naphtho[1,2, Electrophilic, oxobutyl)

Abstract

Derivatives of natural quinones with biological activities, such as lapachol, ?- and ?-lapachones, have been synthesized and their trypanocidal activity evaluated in vitro in Trypanosoma cruzi cells. All tested compounds inhibited epimastigote growth and trypomastigote viability. Several compounds showed similar or higher activity as compared with current trypanocidal drugs, nifurtimox and benznidazole. The results presented here show that the anti-T. cruzi activity of the ?-lapachone derivatives can be increased by the replacement of the benzene ring by a pyridine moiety. Free radical production and consequently oxidative stress through redox cycling or production of electrophilic metabolites are the potential biological mechanism of action for these synthetic quinones. © 2007 Elsevier Ltd. All rights reserved.

Más información

Título de la Revista: BIOORGANIC AND MEDICINAL CHEMISTRY
Volumen: 16
Número: 2
Editorial: Elsevier
Fecha de publicación: 2008
Página de inicio: 668
Página final: 674
URL: http://www.scopus.com/inward/record.url?eid=2-s2.0-38749103884&partnerID=q2rCbXpz