Background: The conjugates of antibiotics are new molecules that might show new antibacterial
spectrum and overcome resistance of insusceptible bacterial strains. Modification of
known antibiotics like Clarithromycin with active fragments is laborious and proven method to
overcome resistance of such strains.
Methods: The conjugates of Clarithromycin and Benzo[c][1,2]oxaboroles were synthesized using
long linkers to extend antimicrobial spectrum of this antibiotic.
Results and Discussion: Unexpected intramolecular deboronation of these bioconjugated was
found to occur when the linker contained two or more CH2-groups. Molecular modeling was used
to understand the source of instability and show a possibility of intramolecular complex of carbonyl
group at C-9 in Clarithromycin core and hydroxy-borole moiety. This could facilitate nucleophilic
attack of methanol used in reactions to destroy benzo[c][1,2]oxaboroles fragments and
leave stable hydroxyl-aryl molecules.
Conclusion: The loss of boron from benzo[c][1,2]oxoborole fragments leads to the significant decrease
of antimicrobial activity of synthesized antibiotics.
Keywords: Macrolactone, macrolide, clarithromycin, benzoxaborole, 1-hydroxy-1, 3-dihydroben-zo[c][1, 2]oxaborole, antibacterial,
conjugates of antibiotics, deboronation.
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