Antimicrobial activity of 8-alkyl- and 8-phenyl-substituted berberines and their 12-bromo derivatives.
The 8-alkyl- (3-6), 8-phenyl- (7), 12-bromo- (8), 8-alkyl-12-bromo- (9-12), and 12-bromo-8-phenyl- (13) berberine derivatives were prepared and tested for their antimicrobial activity in vitro to evaluate structure-activity relationships. Introduction of the alkyl or phenyl group and the bromine atom into the C-8 and C-12 positions of berberine (1), respectively, led to significant increases of the antimicrobial activity. In both the 8-alkyl- and 8-alkyl-12-bromo-berberines (3-6 and 9-12, respectively), the antibacterial activity increased as the length of the aliphatic chain increased. The exception was the activity against Candida albicans and Escherichia coli, which did not always increase as the alkyl side chain lengthened. Among the compounds tested, 12-bromo-8-n-hexylberberine (12) was 64, 256, 128, 16, and 32 times more active against Staphylococcus aureus, Bacillus subtilis, Salmonella enteritidis, E. coli, and C. albicans, respectively, in comparison to the clinically used berberine. Compound 12 was also found to be 8, 16, and 128 times more active against S. aureus, S. enteritidis, and C.albicans, respectively, than kanamycin sulfate, but was of the same order of activity against B. subtilis, and only one-fourth as active against E. coli.
Iwasa
K
K
Kobe Pharmaceutical University, 4-19-1 Motoyamakita, Higashinada-ku, Kobe 658-8558, Japan. K-iwasa@kobepharma-u.ac.jp
Lee
D U
DU
Kang
S I
SI
Wiegrebe
W
W
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D001599:Berberine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D005658:Fungi / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008826:Microbial Sensitivity Tests; D013056:Spectrophotometry, Ultraviolet
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D001599:Berberine