Miroshnyk Inna, Mirza Sabiruddin, Zorky Petr M, Heinämäki Jyrki, Yli-Kauhaluoma Jari, Yliruusi Jouko
Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki, Finland, PO Box 56, FI 00014, Finland.
Bioorg Med Chem. 2008 Jan 1;16(1):232-9. doi: 10.1016/j.bmc.2007.09.044. Epub 2007 Sep 29.
Quantitative analysis of the molecular conformations of the 14-membered macrolide antibiotics erythromycin A and B, clarithromycin, and roxithromycin in the solid state was performed. While the erythronolide macrocycle adopts a very similar folded-out conformation in all the macrolides studied, the proximity of the monosaccharide moieties, L-cladinose and D-desosamine, to each other is demonstrated to be the distinctive feature of their molecular conformations, based on atom-atom interaction energy analysis. More surprisingly, the common features in the relative orientation of the monosaccharide moieties (in terms of non-bonded atom-atom interactions) were revealed between the 14- and 15-membered (azithromycin) macrolide antibiotics. Herein we report on the details of the spatial arrangement of the monosaccharide moieties in these structurally related drug molecules and their influence on the biopharmaceutical properties of erythromycin derivatives.
对14元大环内酯类抗生素红霉素A和B、克拉霉素和罗红霉素的固态分子构象进行了定量分析。虽然在所有研究的大环内酯类药物中，红霉内酯大环都采用非常相似的展开构象，但基于原子-原子相互作用能分析，单糖部分L-克拉定糖和D-脱氧氨基糖彼此之间的接近程度被证明是其分子构象的独特特征。更令人惊讶的是，在14元和15元（阿奇霉素）大环内酯类抗生素之间发现了单糖部分相对取向的共同特征（就非键合原子-原子相互作用而言）。在此，我们报告了这些结构相关药物分子中单糖部分的空间排列细节及其对红霉素衍生物生物药剂学性质的影响。
