engleski

STRUCTURE AND INTERACTIONS OF AZITHROMYCIN- THIOSEMICARBAZONE CONJUGATES AS SEEN BY NMR

Macrolides belong to well-known class of antimicrobial agents widely prescribed to treat upper and lower respiratory tract infections. Azithromycin is a semi-synthetic 15-membered macrolide antibiotic derived from erythromycin possessing broad spectrum of antibacterial potency and favourable pharmacokinetics. However, bacterial resistance to marketed antibiotics is growing rapidly and represents one of the major hazards to human health worldwide. Today, there is a high need for discovery of new antibiotics to combat resistance. Novel conjugates of azithromycin and thiosemicarbazones, the macrozones, represent one such class that exhibits promising activities against resistant pathogens. Solution and solid-state structures of several macrozones have been studied and characterised by one- and two-dimensional NMR spectroscopy. Free and ribosome-bound conformations were further evaluated for selected macrozones with highest bioactivity. Saturation transfer difference (STD), WaterLogsy and transferred nuclear Overhauser effect (trNOE) NMR experiments coupled with molecular modelling studies provided valuable data about binding epitopes and bound conformations. The presented results serve as a good platform for discovery and design of new antiinfectives with improved overall biological effect.

macrolides, macrozones, STD, WaterLogsy, binding epitopes

nije evidentirano