Structure-activity relationship of truncated analogs of caprazamycins as potential anti-tuberculosis agents.
Hirano S, Ichikawa S, Matsuda A.
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'-beta-O-aminoribosyl-glycyluridine class of antibiotics including the CPZs.