Antimicrobial activity of trifluoromethyl ketones and their synergism with promethazine

The antimicrobial effects of 30 trifluoromethyl ketones 1-30] were studied on various representative bacteria. Of the ketones, 4,4,4-trifluoro-1-phenyl-1,3-butanedione 10], 1,1,1-trifluoro-3-(4,5-dimethyloxazol-2-yl)-2-propanone 11] and 1-(2-benzoxazolyl)-3,3,3-trifluoro-2-propanone 18] were found to exhibit potent antibacterial activity against the Gram-positive Bacillus megaterium and Corynebacterium michiganese, but not against Gram-negative bacteria such as Pseudomonas aeruginosa and Serratia marcescens. Compounds 11 and 18 inhibited the Escherichia coli. Compound 18 was also effective against yeasts. The combination of promethazine with 18 was significantly synergistic against E. coli strains, especially the proton pump deficient mutant. The results suggest that membrane transporters are the target of trifluoromethyl ketones. The inhibition was more marked in the proton pump deficient E. coli mutant than in the wild type, which suggested that the antibacterial effect of trifluoromethyl ketones is partly prevented by the proton pump system.