In vitro and in vivo evaluation of quinoxaline 1,4-di-n-oxide against giardia lamblia

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. Conclusions: 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.