The document discusses monobactam antibiotics, focusing on sulfazecin and aztreonam, detailing the structural characteristics that affect their antibacterial activity and stability against β-lactamases. It highlights the development of tigemonam, an orally active monobactam with a spectrum of activity similar to aztreonam, particularly effective against gram-negative bacteria. The document emphasizes the importance of specific chemical groups in enhancing antibacterial potency and resistance to enzymes.

1. MONOBACTAMS
Dr. Shilpa Sudhakar Harak
Asst. Prof., Pharm. Chem.,
GES Sir Dr. M. S. Gosavi College of Pharmaceutical Education and Research, Nashik

2. 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

3. 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.

4. 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.

5. 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.

6. Ceftazidime Vs Aztreonam

7. 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.