World Journal of
Pharmaceutical and Life Sciences

MOLECULAR DOCKING, SYNTHESIS AND BIOLOGICAL EVALUATION FOR NEW 2-ARYL THIAZOLIDINE-4-CARBOXYLIC ACID DERIVATIVES AS Β-LACTAMASE INHIBITORS

Ahmed A. J. Mahmood, Faris T. Abachi* and Mohammed A. Al-Iraqi

ABSTRACT

? -lactam antibiotics have become the standard treatment for bacterial infections. Production of ?-lactamases as the major cause of bacterial resistance inactivates the ?-lactams. There is an urgent need to design and develop anti ? -lactamases (clavulanic acid-like) products. TEM-1 is a prevalent plasmid-encoded ?-lactamase bacterium that efficiently catalyzes the hydrolysis of penicillin and early cephalosporin. Depending on the docking study with TEM-1 ?-lactamase, we synthesize 8 compounds of 2-Aryl thiazolidine- 4-carboxylic acid derivatives (from condensing aromatic aldehydes with L- cysteine). The synthesized compounds were characterized using physical and spectroscopic methods. The biological activity of the 8 new compounds was tested in vitro and their MIC was evaluated against 4 strains of ?-lactamase G(+)ve and G(-)ve pathogenic bacteria, then the anti ?-lactamases activities were tested and compared with that of clavulanic acid as a co-inhibitory with amoxicillin. The results of the biological activity revealed that 3 of them showed anti ?-lactamase effect comparable to that of clavulanic acid. Our results revolve that the ?-lactamase active pocket has hydrophobic space which prefers hydrophobic substituents, as products with these group show the highest affinity.

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