title: Exploring the interplay of physicochemical properties, membrane permeability and giardicidal activity of some benzimidazole derivatives.
abstract: This study evaluated the relationship between the physicochemical properties, membrane permeability and in vitro giardicidal activity of twenty nine benzimidazole derivatives (1-7n). The retention time data from reverse phase high performance chromatography (RP-HPLC) were used to estimate aqueous solubility and lipophilicity of these compounds. The apparent permeability was determined using Caco-2 cell monolayer. The calculation of some descriptors, such as Clog P, PSA, was performed using ACD labs software. For benzimidazole derivatives with NHCOOCH(3), CH(3), NH(2), SH and SCH(3) groups at the 2-position, a quadratic type of regression model was obtained with giardicidal activity and aqueous solubility or lipophilicity. On the other hand, giardicidal activity of 2-(trifluoromethyl)-1H-benzimidazole derivatives was influenced by lipophilicity, hydrogen bond donors and molecular volume but it was not determined by their apparent permeability in Caco-2 cell line.
authors.affiliation: Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, México, DF 04510, Mexico.
authors.forename: Carlos
authors.initials: C
authors.lastname: Hernández-Covarrubias
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Vilchis-Reyes
authors.forename: Lilian
authors.initials: L
authors.lastname: Yépez-Mulia
authors.forename: Remedios
authors.initials: R
authors.lastname: Sánchez-Díaz
authors.forename: Gabriel
authors.initials: G
authors.lastname: Navarrete-Vázquez
authors.forename: Alicia
authors.initials: A
authors.lastname: Hernández-Campos
authors.forename: Rafael
authors.initials: R
authors.lastname: Castillo
authors.forename: Francisco
authors.initials: F
authors.lastname: Hernández-Luis
mesh_terms: D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability; D055598:Chemical Phenomena; D004386:Duodenum / Q000469:parasitology; D016829:Giardia lamblia / Q000187:drug effects*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007583:Jejunum / Q000469:parasitology; D012995:Solubility; D053058:Trophozoites / Q000187:drug effects; D014867:Water / Q000737:chemistry
chemical_list: D000981:Antiprotozoal Agents; D001562:Benzimidazoles; D014867:Water; C031000:benzimidazole