Title:In vitro and In Vivo Evaluation of Quinoxaline 1,4-di-N-oxide Against Giardia lamblia
Volume: 17
Issue: 4
Author(s): Elizabeth Barbosa-Cabrera, Rosa Moo-Puc, Antonio Monge, Alma Delia Paz-González, Virgilio Bocanegra-García and Gildardo Rivera*
Affiliation:
- Laboratorio de Biotecnologia Farmaceutica, Centro de Biotecnologia Genomica, Instituto Politecnico Nacional, Reynosa 88710,Mexico
Keywords:
Biological evaluation, drugs, esters, giardiasis, antiprotozoal, quinoxaline 1, 4-di-N-oxide.
Abstract:
Background: Giardiasis is an important public health problem. However, its
pharmacological treatment is limited mainly to two drugs, metronidazole and nitazoxanide.
Objectives: Screening four series of esters (methyl, ethyl, isopropyl and n-propyl) of quinoxaline-7-
carboxylate 1,4-di-N-oxide in in vitro and in vivo models as antigiardiasis agents.
Methods: Briefly, 4 × 104 trophozoites of G. lamblia were incubated for 48 h at 37 °C with different
concentrations of esters of quinoxaline-7-carboxylate 1,4-di-N-oxide, albendazole, metronidazole
and nitazoxanide. Afterwards, trophozoites were counted and the half maximal inhibitory
concentration (IC50) was calculated by Probit analysis. The in vivo antigiardial activity of the
compounds was demonstrated using experimental infections of G. lamblia in suckling female CD-1
mice.
Results: Compound T-069 with a thienyl, a trifluoromethyl and an isopropyl group at R1-, R2- and
R3-position, respectively, on the quinoxaline 1,4-di-N-oxide ring in an in vitro model showed an IC50
value of 0.0014 µM, and 3502 and 1108 times more giardicidal activity than nitazoxanide and
metronidazole in an in vivo model.
Conclusion: Isopropyl ester of quinoxaline-7-carboxylate 1,4-di-N-oxide derivatives showed better
giardicidal activity than the reference drugs; therefore, these compounds are good candidates to
develop new pharmacological treatment for giardiasis.
