الفهرس 
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Abstract
Background: The present study deals with the synthesis of new thirty-three compounds of thiazole derivatives bearing chloroacetyl, thiazolidinone, thiourea, phenylamide or phenylsulfonyl motifs, in addition to six compounds combining thiazole/imidazole or thiazole/pyrimidine were synthesized and screened for their potential antimicrobial activity. Method: includes the synthetic procedures of the designed compounds as well as the physicochemical and spectral data of the prepared compounds and the in vitro biological screening of the newly synthesized compounds against selected bacterial and fungal strains, the E.coli DNA gyrase, the S. aureus topoisomerase IV, and DHFR enzymes. Results: Compounds 55c, 57c, 59aand 60dshowed good binding and dual inhibition against both enzymes E.coli DNA gyrase and the S. aureus topoisomerase IV. compound 58 was selected for the assessment of its binding affinity and enzyme inhibitory activity against activity against dihydrofolate reductase (DHFR). It showed results better than that of the reference drug sulfathiazole. Hence, it may serve as an important lead for discovery of novel DHFR inhibitors. In silico studies revealed a potential good oral absorption of compounds Conclusion: compounds 59a-d exhibited antibacterial activity against the tested Gram negative strains Compounds (57c, 60d) and 59arevealed the best results against the E.coli DNA gyrase and the S. aureus topoisomerase IV, respectively. Compound 58 may serve as an important lead for discovery of novel DHFR inhibitor. The active compounds in this study especially 57c, 58, 59aand 60dare good candidates for further modifications to develop new more effective antibacterial agents.