A new insight into solid-state conformation of macrolide antibiotics.
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.
Miroshnyk
Inna
I
Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki, Finland, PO Box 56, FI 00014, Finland. inna.miroshnyk@helsinki.fi
Mirza
Sabiruddin
S
Zorky
Petr M
PM
Heinämäki
Jyrki
J
Yli-Kauhaluoma
Jari
J
Yliruusi
Jouko
J
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
D000900:Anti-Bacterial Agents; D018942:Macrolides; D009005:Monosaccharides; D015575:Roxithromycin; D004917:Erythromycin; D017291:Clarithromycin