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Monobactum

The document provides an overview of monobactams, a class of β-lactam antibiotics, highlighting their structure, synthesis, and antibacterial properties. Aztreonam, the key monobactam discussed, is exclusively effective against gram-negative bacteria and shows resistance to β-lactamases. The document also compares aztreonam with newer monobactams like tigemonam, emphasizing their clinical relevance and spectrum of activity.

Health & Medicine◦
MONOBACTAMS Dr. Shilpa Sudhakar Harak Asst. Prof., Pharm. Chem., GES Sir Dr. M. S. Gosavi College of Pharmaceutical Education and Research, Nashik
Beta-lactam  A beta-lactam (β-lactam) ring is a four-membered lactam.  A lactam is a cyclic amide, and beta-lactams are named so because the nitrogen atom is attached to the β-carbon atom relative to the carbonyl.  The simplest β-lactam possible is 2-azetidinone.
Types of Lactam
Basic ring nomenclature
Sulfazecin  First isolated useful monobactam antibiotics from saprophytic soil bacteria  Weakly active as an antibacterial agent  Highly resistant to β-lactamases.  SAR studies eventually led to the development of aztreonam
Sulfazecin  SAR studies eventually led to the development of aztreonam  3-methoxy group - responsible for β-lactamase stability in the series,  contributed to the low antibacterial potency & poor chemical stability of these antibiotics.  4-methyl group –  increases stability to β-lactamases and  increases activity against Gram-negative bacteria  potency against Gram-positive bacteria decreases.  4,4-Gem-dimethyl substitution –  slight decrease in antibacterial potency after oral administration.
Aztreonam  Monocyclic β-lactam antibiotic  Natural molecules served as the inspiration for the synthesis  Totally synthetic parenteral antibiotic  Exclusively active towards gram-negative microorganisms,  Inactivates some β-lactamases.  MOA similar to that of the penicillins, cephalosporins, and carbapenems,  Has strong affinity for PBP-3, producing filamentous cells as a consequence.
Aztreonam Structure Similarity:  The C3 sulfamic acid moiety attached to the β-lactam ring similar to ceftazidime.  The sulfur at N1 is similar to C-2 carboxyl group of β-lactam antibiotics to confuse the PBPs.  The strongly EW group - sulfamic acid group makes the β-lactam bond more vulnerable to hydrolysis.  The monobactams demonstrate that a fused ring is not essential for antibiotic activity.  The α-oriented methyl group at C-2 is associated with the stability of aztreonam toward β-lactamases.
Ceftazidime Vs Aztreonam Ceftazidime
Tigemonam  Newer monobactam that is orally active.  It is highly resistant to β-lactamases.  The antibacterial spectrum of activity resembles that of aztreonam.  It is very active against the Enterobacteriaceae, including E. coli, Klebsiella, Proteus, Citrobacter, Serratia and Enterobacter spp.  It also exhibits good potency against H. influenzae and N. gonorrhoeae.  Tigemonam is not active against Gram-positive or anaerobic bacteria and is inactive against P. aerugi  The oral absorption of tigemonam is excellent.  It could become a valuable agent for the oral treatment of UTI and other non–life-threatening infections caused by beta-lactamase– producing Gram-negative bacteria.
For more details on  Mode of Action pharmacophores  responsible for activity of monobactams  refer slideshare presentation for Penicillin Antibiotics @  https://www.slideshare.net/shilpa1980/penicillin-237643170