Microwave induced synthesis of fluorobenzamides containing thiazole and thiazolidine as promising antimicrobial analogs

Abstract

New 5-arylidene derivatives, which bear a fluorine atom in the 4th position of the benzoyl group as starting compound, have been synthesized by the condensation of 4-fluoro-N-(4-methyl-5-(2-(4-oxo-3-phenylthiazolidin-2-ylidene)hydrazinecarbonyl)thiazol-2-yl)benzamide and Knoevenagel condensation with aromatic aldehydes to form N-(5-(2-(5-(arylidene)-4-oxo-3-phenylthiazolidin-2-ylidene)hydrazinecarbonyl)-4-methylthiazol-2-yl)-4-fluorobenzamides (6a–o) through conventional and microwave methods. The structures of synthesized compounds were established by spectroscopic as well as spectrometric techniques (IR, 1H NMR, 13C NMR, 19F NMR spectroscopy and mass spectrometry). Antimicrobial screening of 5-arylidene derivatives 6a–o was done against Gram-positive bacteria (Staphylococcus aureus and Streptococcus pyogenes), Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) and fungi (Candida albicans, Aspergillus niger, and Aspergillus clavatus) using serial broth dilution method. Compounds 6g and 6j were found to be most active at MIC 12.5μg/mL against selected bacterial strains and compound 6e was found to be most active at MIC 25μg/mL against selected fungal strains. It has been further observed that the presence of fluorine atom at the 4th position of the benzoyl group in the final compounds is essential for enhancing the antimicrobial activity.