Exploring the interplay of physicochemical properties, membrane permeability and giardicidal activity of some benzimidazole derivatives

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 NHCOOCH3, CH3, NH2, SH and SCH3 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.

Figure optionsDownload as PowerPoint slideHighlights
► Benzimidazole with CF3 group showed different correlations to other compounds.
► Caco-2 BA/AB, HBA and HBD determined the giardicidal activity of some compounds.
► Aqueous solubility and lipophilicity were determined by retention time from RP-HPLC.
► Log D of benzimidazole tautomers or regioisomers were determined by RP-HPLC.