title: A new insight into solid-state conformation of macrolide antibiotics.
abstract: 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.
authors.affiliation: Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki, Finland, PO Box 56, FI 00014, Finland. inna.miroshnyk@helsinki.fi
authors.forename: Inna
authors.initials: I
authors.lastname: Miroshnyk
authors.forename: Sabiruddin
authors.initials: S
authors.lastname: Mirza
authors.forename: Petr M
authors.initials: PM
authors.lastname: Zorky
authors.forename: Jyrki
authors.initials: J
authors.lastname: Heinämäki
authors.forename: Jari
authors.initials: J
authors.lastname: Yli-Kauhaluoma
authors.forename: Jouko
authors.initials: J
authors.lastname: Yliruusi
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D017291:Clarithromycin / Q000737:chemistry; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000737:chemistry; D018942:Macrolides / Q000737:chemistry*; D008968:Molecular Conformation; D009005:Monosaccharides; D015575:Roxithromycin / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides; D009005:Monosaccharides; D015575:Roxithromycin; D004917:Erythromycin; D017291:Clarithromycin