Antimicrobial activity of trifluoromethyl ketones and their synergism withpromethazine

The antimicrobial effects of 30 trifluoromethyl ketones [1-30] were studied on various representative bacteria. Of the ketones, 4,4,4-trifluoro-1-phen yl-1,3-butanedione [10], 1,1,1-trifluoro-3-(4,5-dimethyloxazol-2-yl)-2-prop anone [11] and 1-(2-benzoxazolyl)-3,3,3-trifluoro-2-propanone [18] were fou nd to exhibit potent antibacterial activity against the Gram-positive Bacil lus megaterium and Corynebacterium michiganese, but not against Gram-negati ve bacteria such as Pseudomonas aeruginosa and Serratia marcescens. Compoun ds 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 m utant. The results suggest that membrane transporters are the target of tri fluoromethyl ketones. The inhibition was more marked in the proton pump def icient E. coli mutant than in the: wild type;, which suggested that the ant ibacterial effect of trifluoromethyl ketones is partly prevented by the pro ton pump system. (C) 2001 Elsevier Science B.V. and International Society o f Chemotherapy. All rights reserved.