Abstract:
:Antibiotic-resistant bacteria are emerging at an alarming rate in both hospital and community settings. Motivated by this issue, we have prepared desmethyl (i.e., replacing methyl groups with hydrogens) analogues of third-generation macrolide drugs telithromycin (TEL, 2) and cethromycin (CET, 6), both of which are semi-synthetic derivatives of flagship macrolide antibiotic erythromycin (1). Herein, we report the total synthesis, molecular modeling, and biological evaluation of 4,8,10-tridesmethyl cethromycin (7). In MIC assays, CET analogue 7 was found to be equipotent with TEL (2) against a wild-type E. coli strain, more potent than previously disclosed desmethyl TEL congeners 3, 4, and 5, but fourfold less potent than TEL (2) against a mutant E. coli A2058G strain.
journal_name
ACS Med Chem Lettjournal_title
ACS medicinal chemistry lettersauthors
Wagh B,Paul T,Debrosse C,Klepacki D,Small MC,Mackerell AD Jr,Andrade RBdoi
10.1021/ml400337tsubject
Has Abstractpub_date
2013-11-14 00:00:00pages
1114-1118issue
11issn
1948-5875journal_volume
4pub_type
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