title: In vitro anti-Giardia lamblia activity of 2-aryl-3-hydroxymethyl imidazo[1,2-a]pyridines and -pyrimidines, individually and in combination with albendazole.
abstract: Giardiasis is a major diarrheal disease found throughout the world, the causative agent being the flagellate protozoan Giardia intestinalis. Infection is more common in children than in adults. The appearance of drug resistance has complicated the treatment of several parasitic diseases, including giardiasis. Thus, the aim of this investigation was to make an in vitro evaluation of the antigiardia response of synthetic derivatives 2-aryl-3-hydroxymethylimidazo[1,2-a]pyridines 1 and -pyrimidines 2 against trophozoites of Giardia lamblia WB, in comparison with the reference drug, albendazole. Additionally, the synergistic action of albendazole in combination with each of the most active 2-aryl-3-hydroxymethyl imidazo[1,2-a]pyridines and pyrimidines was also assessed. Based on the IC50 values obtained, the best anti-Giardia activity was provided by the 3-hydroxymethyl-4-fluorophenylimidazo[1,2-a]pyrimidine derivative 2c and the corresponding imidazo[1,2-a]pyrimidine with the p-tolyl substituent 2d, followed by 2a and 2b. These four compounds showed effectiveness at a concentration similar to that of albendazole. Regarding synergism, the IC50 of the combination of albendazole with 2a, 2b or 2c gave the best anti-Giardia action, showing greater efficacy than albendazole alone. Hence, G. lamblia WB showed high susceptibility to some 2-aryl-3-hydroxymethyl imidazo[1,2-a] pyrimidines, which acted synergistically when used in combination with albendazole.
authors.affiliation: Departamento Química Orgánica, Escuela Nacional Ciencias Biológicas, Instituto Politécnico Nacional, Prolongación de Carpio y Plan de Ayala s/n, Col. Santo Tomas, 11340 México City, Mexico. Electronic address: steffivel@hotmail.com.
authors.forename: Stephanía
authors.initials: S
authors.lastname: Velázquez-Olvera
authors.affiliation: Departamento Química Orgánica, Escuela Nacional Ciencias Biológicas, Instituto Politécnico Nacional, Prolongación de Carpio y Plan de Ayala s/n, Col. Santo Tomas, 11340 México City, Mexico. Electronic address: hsalgado@ipn.com.
authors.forename: Héctor
authors.initials: H
authors.lastname: Salgado-Zamora
authors.affiliation: Laboratorio de Investigación en Parasitología, Hospital Infantil de Mexico "Federico Gomez", SS, Dr. Marquez No. 162, Col. Doctores, 06720 Mexico City, Mexico. Electronic address: enedina@unam.mx.
authors.forename: Enedina
authors.initials: E
authors.lastname: Jiménez-Cardoso
authors.affiliation: Departamento Química Orgánica, Escuela Nacional Ciencias Biológicas, Instituto Politécnico Nacional, Prolongación de Carpio y Plan de Ayala s/n, Col. Santo Tomas, 11340 México City, Mexico. Electronic address: camesol22@gmail.com.
authors.forename: Maria-Elena
authors.initials: ME
authors.lastname: Campos-Aldrete
authors.affiliation: Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana Xochimilco, Calzada del Hueso 1100, Col. Villa Quietud, 04960 Mexico City, Mexico. Electronic address: cperezg@correo.xoc.uam.mx.
authors.forename: Cuauhtémoc
authors.initials: C
authors.lastname: Pérez-González
authors.affiliation: Laboratoire Chimie Matériaux, Département de Chimie, Faculté des Sciences, Université Mohamed 1ER, 60000 Oujda, Morocco. Electronic address: taibi.ben.hadda@gmail.com.
authors.forename: Taibi
authors.initials: T
authors.lastname: Ben Hadda
mesh_terms: D015766:Albendazole / Q000494:pharmacology*; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D004357:Drug Synergism; D016829:Giardia lamblia / Q000187:drug effects*; D005873:Giardiasis / Q000188:drug therapy*; D006801:Humans; D020128:Inhibitory Concentration 50; D011725:Pyridines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*
chemical_list: D000981:Antiprotozoal Agents; D011725:Pyridines; D011743:Pyrimidines; D015766:Albendazole
keywords: 2-aryl-3-hydroxymethyl imidazo[1,2-a]pyridines and -pyrimidines; Albendazole; Anti-Giardia; In vitro susceptibility; Synergism