title: The structure-bioavailability approach in antifungal agents.
abstract: The thermodynamic and electrostatic properties of antifungal triazole and imidazole derivatives: itraconazole, fluconazole, miconazole and ketoconazole molecules were calculated. The main aim of our investigations was to identify molecular determinants that have an effect on bioavailability of studied compounds. This is solvation energy estimated by the DeltaG values as well as electrostatic properties of the molecules. The influence of another substituents was also considered. The presented values are discriminative and reflect very low solubility of ketoconazole in water in comparison with other molecules. The thermodynamic and electrostatic properties of molecules appeared to be good indicators of bioavailability of compounds studied here and they are likely to be used as screening parameters in Biopharmaceutical Classification System (BCS) development.
authors.affiliation: Department of Drug Chemistry, Warsaw Medical University, 1 Banacha Str., 02-097 Warsaw, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Grudzień
authors.forename: Anna
authors.initials: A
authors.lastname: Król
authors.forename: Grazyna
authors.initials: G
authors.lastname: Paterek
authors.forename: Karolina
authors.initials: K
authors.lastname: Stepień
authors.forename: Franciszek
authors.initials: F
authors.lastname: Pluciński
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Mazurek
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D015195:Drug Design; D007093:Imidazoles / Q000737:chemistry / Q000493:pharmacokinetics*; D021281:Quantitative Structure-Activity Relationship; D055672:Static Electricity; D013816:Thermodynamics; D014230:Triazoles / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D000935:Antifungal Agents; D007093:Imidazoles; D014230:Triazoles