Abstract:
Antimicrobial resistance has become a major public health challenge, aggravating
morbidity and mortality, complicating the treatment of bacterial infections and putting
immense pressure on health systems. In this study, we have synthesized new antimicrobial
agents by the β-lactam antibiotics with sulfonamide moieties to achieve high antibacterial
efficacy with a wider range of action. Newly synthesized compounds were developed by
reacting solid β-lactam compounds (Cephalosporin) with sulfonyl chloride (Benzene
sulfonyl chloride and methanesulfonyl chloride), at equal amounts under controlled
conditions. The elucidation of newly synthesized compounds was performed by using
HPLC, FTIR and NMR spectroscopic techniques which confirmed the formation of newly
synthesized compounds. After the chemical confirmation, the antimicrobial efficacy of the
newly synthesized compounds was evaluated against a panel of Gram-positive and Gram-
negative bacteria, indicating promising Minimum Inhibitory Concentration (MIC) values.
Among all compounds, compound 4b showed the lowest MIC (16 µg/ml) against all
microorganisms tested, suggesting to be a potent antimicrobial agent. Assays for zone of
inhibition were also performed which also indicated the promising antimicrobial effects of
the newly synthesized compounds against bacterial growth. All compounds showed the
zone of inhibition in the range of 1.3mm-1.5mm against P.aeruginosa, S.aureus, E.coli,
and B.subtilis. Furthermore, molecular docking studies indicated the interactions of these
compounds with the penicillin-binding proteins (1vqq) and suggest possible mechanisms
of action involving hydrogen bonds with key amino acid residues (ASP667, HIS351,
GLU356). The in-silico pharmacokinetic analysis suggested that most compounds
demonstrate drug-like properties to provide a rational basis for future development as oral
active drug candidates.