Monobactams Chemische Eigenschaften,Einsatz,Produktion Methoden
Antimicrobial activity
Study of the structural basis of activity of early β-lactam
compounds led to the expectation that compounds in which
the β-lactam ring was not strained by fusion to another ring
would be inactive as antimicrobial agents. However, some
natural monocyclic β-lactam antibiotics, including certain
monobactams and nocardicins, are active in vitro against
Gram-negative bacteria, including Ps. aeruginosa.
In contrast to penicillins and cephalosporins, which are commonly
produced by fungi and actinomycetes, naturally occurring
monobactams are produced by bacteria. Because of their simplicity
of structure, they can be obtained easily by total synthesis. In some
monobactams the β-lactam ring carries an α-methoxy group, similar
to the β-lactamase-stable cephamycins, but the first monobactam
used therapeutically, and the only one to achieve modest
commercial acceptability, aztreonam, lacks this substituent.
Monobactams exhibit no useful activity against Grampositive
organisms or strict anaerobes because of poor binding
to PBPs . Activity against Gram-negative bacteria,
including Ps. aeruginosa, is due to tight binding to PBP 3
(Esch. coli numbering). As a result, the organisms convert to
filaments, which slowly lyse.
Monobactams are hydrolyzed poorly by many serine
β-lactamases and all metallo-β-lactamases, but can be hydrolyzed
by ESBLs and serine carbapenemases. Group 1 cephalosporinases
have high affinities for non-methoxylated
monobactams, whereas group 2 β-lactamases generally bind
aztreonam poorly. They are generally not inducers of the group
1 chromosomal cephalosporinases of Gram-negative bacteria.
Monobactams Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
