Trypanosoma cruzi: activities of lapachol and alpha- and beta-lapachone derivatives against epimastigote and trypomastigote forms.
Derivatives of natural quinones with biological activities, such as lapachol, alpha- and beta-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 alpha-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.
Salas
Cristian
C
Departamento de Química Orgánica, Facultad de Química, Pontificia Universidad Católica de Chile, Av. Vicuña Mackenna 4860, Macul, Santiago 6094411, Chile. cosalas@uc.cl
Tapia
Ricardo A
RA
Ciudad
Karina
K
Armstrong
Verónica
V
Orellana
Myriam
M
Kemmerling
Ulrike
U
Ferreira
Jorge
J
Maya
Juan Diego
JD
Morello
Antonio
A
D000818:Animals; D015394:Molecular Structure; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010084:Oxidation-Reduction; D013237:Stereoisomerism; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects*
D009285:Naphthoquinones; D014344:Trypanocidal Agents; C014638:beta-lapachone; C008252:lapachol; C415043:alpha-lapachone