Conjoint molecules of cephalosporins and aminoglycosides.

A general synthetic route to conjoint molecules of cephalosporins and aminoglycosides is described. These molecules were designed as potential substrates for bacterial beta-lactamases, enzymes that hydrolyze the beta-lactam bond of cephalosporins. Hydrolysis of the beta-lactam bond was expected to release the C10-appended aminoglycoside. Since beta-lactamases are sequestered in the periplasmic space of gram-negative bacteria, this sequence of events would liberate aminoglycoside inside such bacteria. It is expected that such local delivery of aminoglycosides would circumvent the inherent toxicity of aminoglycosides that occurs during systemic exposure within the mammalian host.