Abstract:
:Novel sources of antibiotics are required to keep pace with the inevitable onset of bacterial resistance. Continuing with our macrolide desmethylation strategy as a source of new antibiotics, we report the total synthesis, molecular modeling and biological evaluation of 4,10-didesmethyl telithromycin (4), a novel desmethyl analogue of the 3rd-generation drug telithromycin (2). Telithromycin is an FDA-approved ketolide antibiotic derived from erythromycin (1). We found 4,10-didesmethyl telithromycin (4) to be four times more active than previously prepared 4,8,10-tridesmethyl congener (3) in MIC assays. While less potent than telithromycin (2), the inclusion of the C-8 methyl group has improved biological activity suggesting it plays an important role in antibiotic function.
journal_name
ACS Med Chem Lettjournal_title
ACS medicinal chemistry lettersauthors
Velvadapu V,Glassford I,Lee M,Paul T,Debrosse C,Klepacki D,Small MC,Mackerell AD Jr,Andrade RBdoi
10.1021/ml200254hsubject
Has Abstractpub_date
2012-03-08 00:00:00pages
211-215issue
3issn
1948-5875journal_volume
3pub_type
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