Structure–activity relationship of truncated analogs of caprazamycins as potential anti-tuberculosis agents

Systematic structure–activity relationship studies of caprazamycin (CPZ) analogs, including the aminoribose-truncated 5 and the uridine-truncated 6, have been carried out. Both 5 and 6 were synthesized efficiently via diazepanone ring construction by intramolecular reductive alkylation of aminoaldehyde derivatives. The antibacterial activity of a range of analogs, including 5 and 6, against Mycobacteriumosis was evaluated, and it was found that the uridine, the aminoribose, and the fatty acyl side chains are crucial for antibacterial activity. This study would be a guide for designing novel anti-tuberculosis agents based on the 6′-N-alkyl-5′-β-O-aminoribosyl-glycyluridine class of antibiotics including the CPZs.

Synthesis and structure–activity relationship studies of caprazamycin (CPZ) analogs, including the aminoribose-truncated and the uridine-truncated one have been carried out.Figure optionsDownload as PowerPoint slide