Conjoint molecules of cephalosporins and aminoglycosides

✍ Scribed by Ioannis Grapsas; Stephen A. Lerner; Shahriar Mobashery

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 129 KB
• Volume: 334
• Category: Article
• ISSN: 0365-6233
• DOI: 10.1002/1521-4184(200109)334:8/9<295::aid-ardp295>3.0.co;2-3

✦ Synopsis

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 β-lactamases, enzymes that hydrolyze the β-lactam bond of cephalosporins. Hydrolysis of the β-lactam bond was expected to release the C10-appended aminoglycoside. Since β-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.