Bioorganic and Biophysical Chemistry Laboratory, School of Natural Sciences, Linnaeus University, SE-391 82 Kalmar, Sweden.
Biochem Biophys Res Commun. 2011 Apr 8;407(2):318-20. doi: 10.1016/j.bbrc.2011.03.010. Epub 2011 Mar 5.
Warfarin is an important oral anticoagulant drug that demonstrates a molecular-environment dependent structural diversity. Previous investigations of warfarin's ensemble of isomers in organic solvent-based environments have pointed to the importance of the closed-ring cyclic hemiketal form of the drug in non-polar environments, e.g. the interior of proteins, enzymes and biomembranes. Detection of the presence of these isomers in polar environments has not yet been reported. Here, we demonstrate the presence of the cyclic hemiketal structural form of warfarin under aqueous conditions. This finding underscores the importance considering all structural isomers of this drug when making predictions on warfarin's bioavailability.
华法林是一种重要的口服抗凝药物，表现出分子环境依赖的结构多样性。先前对华法林在有机溶剂环境中的异构体混合物的研究表明，在非极性环境（如蛋白质、酶和生物膜的内部）中，药物的闭环环状半缩醛形式非常重要。然而，在极性环境中是否存在这些异构体尚未得到报道。在这里，我们证明了华法林在水相条件下存在环状半缩醛结构形式。这一发现强调了在预测华法林的生物利用度时，考虑到这种药物所有结构异构体的重要性。
