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Conjoint molecules of cephalosporins and aminoglycosides
Author(s) -
Grapsas Ioannis,
Lerner Stephen A.,
Mobashery Shahriar
Publication year - 2001
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/1521-4184(200109)334:8/9<295::aid-ardp295>3.0.co;2-3
Subject(s) - cephalosporin , chemistry , molecule , stereochemistry , combinatorial chemistry , antibiotics , organic chemistry , biochemistry
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 C 10 ‐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.