Studies on beta-D-gal(f)-(1 -> 4)-alpha-L-rha(p) octyl analogues as substrates for mycobacterial galactosyl transferase activity

The biochemically unique structures of sugar residues in the outer cell wal l of Mycobacterium tuberculosis (MTB) make the pathways for their biosynthe sis and utilization attractive targets for the development of new and selec tive anti-tubercular agents. A cell-free assay system for galactosyltransfe rase activity using UDP[C-14]Gal as the glycosyl donor, as well as an in vi tro colorimetric broth micro-dilution assay system, were used to determine the activities of three beta-D-gal(f)(1-->4)-alpha-L-rham(p) octyl disaccha rides as substrates and antimycobacterial agents respectively. The cell-fre e enzymatic studies using compounds 8 and 10 suggested that these disacchar ides bind to and are effective substrates for a putative mycobacterial gala ctosyltransferase. The modified acceptor 8 was found to be a slower but pro longed binder as compared to the less substituted analogue 10 as evidenced by their K-m and V-max values. Moderate antimycobacterial activity was obse rved with compounds 8 and 9 against MTB H37Ra and three clinical isolates o f Mycobacterium avium complex (MAC). (C) 1999 Elsevier Science Ltd. All rig hts reserved.