Synthesis and Antimicrobial Screening of New 5-Aryl-3-(4-Aryl-1,3-Thiazol-2-yl)-1,2-Oxazole Derivatives

A new series of 5-aryl-3-(4-aryl-1,3-thiazol-2-yl)-1,2-oxazole derivatives 12–27 have been efficiently synthesized from 5-aryl-1,2-oxazole-3-carbothioamides 7a–d and 2-bromo-1-aryl ethanone 8–11. Compounds 12–27 were characterized by IR and NMR spectroscopy and mass spectrometry methods. Compounds 12–27 were evaluated for in vitro antimicrobial activity against P. mirabilis, E. coli, S. aureus, B. subtilis, A. niger and C. albicans strains. Amongst the sixteen derivatives, against the P. mirabilis, compounds 12, 14, 16, 17, 18, 20, 21, 22, 23, 24, 26, and 27 exhibited good activity. The SAR exposed that for the 3,4-dimethoxyphenyl group at the C-5 position of the 1,2-oxazole, all four derivatives 20–23 showed good activity against P. mirabilis, which indicates the 3,4-dimethoxyphenyl group is essential for activity. Against the microbial strains E. coli, B. subtilis, S. aureus, A. niger and C. albicans, compounds 12–27 were found less active. The active derivatives were evaluated for cytotoxicity against normal cell line of mouse embryonic fibroblast cells (3T3L1) at 25 and 50 µg/mL concentrations and found non-cytotoxic. These results suggested that the clubbing of the 2-position of the 1,3-thiazole with the 3-position of 1,2-oxazole is less effective for a broad spectrum of activity and needs further modifications.