The structure-bioavailability approach in antifungal agents

被引：12
作者：
Grudzien, Monika [2 ]
Krol, Anna [2 ]
Paterek, Grazyna [2 ]
Stepien, Karolina [2 ]
Plucinski, Franciszek [1 ]
Mazurek, Alexander P. [1 ,2 ]
机构：
[1] Natl Med Inst, PL-00725 Warsaw, Poland
[2] Warsaw Med Univ, Dept Drug Chem, PL-02097 Warsaw, Poland
来源：
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 44卷 / 05期
关键词：
Antifungal agent; BCS system; Bioavailability; STEROL; 14-ALPHA-DEMETHYLASE; RESISTANCE; CYP51; MECHANISMS; TARGETS; P450;
D O I：
10.1016/j.ejmech.2008.10.028
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
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 Delta G 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. (C) 2008 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码：1978 / 1981
页数：4
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