Elizabeth Barbosa-Cabrera, Rosa Moo-Puc, Antonio Monge, Alma Delia Paz-González, Virgilio Bocanegra-García and Gildardo Rivera* Pages 428 - 433 ( 6 )
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.
Biological evaluation, drugs, esters, giardiasis, antiprotozoal, quinoxaline 1, 4-di-N-oxide.
Escuela Superior de Medicina, Instituto Politecnico Nacional, Ciudad de México 11340, Unidad de Investigacion Medica Yucatan, Unidad Medica de Alta Especialidad, Centro Médico Ignacio Garcia Tellez, Instituto Mexicano del Seguro Social, Col. Industrial, 97150 Merida, Yucatan, Neglected Diseases Section, Drug R & D Unit, Center for Applied Pharmacobiology Research, University of Navarra, C/Irunlarrea 1, Pamplona 31008, Laboratorio de Biotecnologia Farmaceutica, Centro de Biotecnologia Genomica, Instituto Politecnico Nacional, Reynosa 88710, Laboratorio de Biotecnologia Farmaceutica, Centro de Biotecnologia Genomica, Instituto Politecnico Nacional, Reynosa 88710, Laboratorio de Biotecnologia Farmaceutica, Centro de Biotecnologia Genomica, Instituto Politecnico Nacional, Reynosa 88710