Two approaches to the use of benzo[c][1,2]oxaboroles as active fragments for synthetic transformation of clarithromycin.

ABSTRACT: Clarithromycin (active against Gram positive infections) and 1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborole derivatives (effective for Gram negative microbes) are the ligands of bacterial RNA. The antimicrobial activities of these benzoxaboroles linked with clarithromycin at 9 or 4? position were compared. Two synthetic pathways for these conjugates were elaborated. First pathway explored the substitution of the C-9 carbonyl group of macrolactone's cycle via oxime linker, the second direction used the modification of the 4?-O-group of cladinose via the formation of carbamates of benzoxaboroles. 4?-O-(3-S-(1-Hydroxy-1,3-dihydro-benzo[c][1,2]oxaborole)-methyl-carbamoyl-clarithromycin showed twofold decrease in MICs for S. epidermidis and S. pneumoniae than clarithromycin. 4?-O-Modified clarithromycin demonstrated an efficacy against Gram positive strains only. Compounds with C-9 substitution were more active than 4?-O-substituted antibiotics for susceptible strains E. coli tolC and did not exceed the activity of initial antibiotics.

SUBMITTER: Lapa GB 

PROVIDER: S-EPMC6009856 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature