AIMS: There is a need for novel treatments for Clostridium difficile infection(CDI). Antibacterial flavonoids are part of a large family of polyphenol phytochemicals with a long history of use in ethnomedicine, but are unexamined against Cl. difficile. We explored their anti-difficile properties. METHODS AND RESULTS: Anti-difficile activities were determined for several naturally occurring flavonoids, olympicin A and synthetic 4-chromanone and chalcone analogues. With the exception of olympicin A, most naturally occurring phytochemicals tested were poorly active. Diversified synthetic flavonoids resembling olympicin A retained anti-difficile activity, suggesting olympicin A could act as a pharmacophore to obtain novel agents. They also demonstrated concentration-dependent killing of logarithmic and stationary phase cultures and reduced sporulation and toxin production. Olympicin A and some synthetic flavonoids dissipated the bacterial transmembrane potential. Interestingly, mutants could only be selected with the analogue 207 at a frequency of 10(-9). CONCLUSIONS: Based on the potent anti-difficile properties of olympicin A and modified flavonoids, further exploration of this class of phytochemicals is warranted. SIGNIFICANCE AND IMPACT OF THE STUDY: Clostridium difficile infection is a major problem in developed countries. These studies point to there being an avenue for optimizing plant-derived flavonoids, and related antibacterial phytochemicals, as nature-inspired approaches to treat CDI.
AIMS: There is a need for novel treatments for Clostridium difficile infection(CDI). Antibacterial flavonoids are part of a large family of polyphenol phytochemicals with a long history of use in ethnomedicine, but are unexamined against Cl. difficile. We explored their anti-difficile properties. METHODS AND RESULTS: Anti-difficile activities were determined for several naturally occurring flavonoids, olympicin A and synthetic 4-chromanone and chalcone analogues. With the exception of olympicin A, most naturally occurring phytochemicals tested were poorly active. Diversified synthetic flavonoids resembling olympicin A retained anti-difficile activity, suggesting olympicin A could act as a pharmacophore to obtain novel agents. They also demonstrated concentration-dependent killing of logarithmic and stationary phase cultures and reduced sporulation and toxin production. Olympicin A and some synthetic flavonoids dissipated the bacterial transmembrane potential. Interestingly, mutants could only be selected with the analogue 207 at a frequency of 10(-9). CONCLUSIONS: Based on the potent anti-difficile properties of olympicin A and modified flavonoids, further exploration of this class of phytochemicals is warranted. SIGNIFICANCE AND IMPACT OF THE STUDY: Clostridium difficile infection is a major problem in developed countries. These studies point to there being an avenue for optimizing plant-derived flavonoids, and related antibacterial phytochemicals, as nature-inspired approaches to treat CDI.
Authors: Michel Warny; Jacques Pepin; Aiqi Fang; George Killgore; Angela Thompson; Jon Brazier; Eric Frost; L Clifford McDonald Journal: Lancet Date: 2005 Sep 24-30 Impact factor: 79.321
Authors: Miao He; Fabio Miyajima; Paul Roberts; Louise Ellison; Derek J Pickard; Melissa J Martin; Thomas R Connor; Simon R Harris; Derek Fairley; Kathleen B Bamford; Stephanie D'Arc; Jon Brazier; Derek Brown; John E Coia; Gill Douce; Dale Gerding; Hee Jung Kim; Tse Hsien Koh; Haru Kato; Mitsutoshi Senoh; Tom Louie; Stephen Michell; Emma Butt; Sharon J Peacock; Nick M Brown; Tom Riley; Glen Songer; Mark Wilcox; Munir Pirmohamed; Ed Kuijper; Peter Hawkey; Brendan W Wren; Gordon Dougan; Julian Parkhill; Trevor D Lawley Journal: Nat Genet Date: 2012-12-09 Impact factor: 38.330
Authors: Philip T Cherian; Xiaoqian Wu; Lei Yang; Jerrod S Scarborough; Aman P Singh; Zahidul A Alam; Richard E Lee; Julian G Hurdle Journal: J Antimicrob Chemother Date: 2015-08-18 Impact factor: 5.790
Authors: Li Feng; Marcus M Maddox; Md Zahidul Alam; Lissa S Tsutsumi; Gagandeep Narula; David F Bruhn; Xiaoqian Wu; Shayna Sandhaus; Robin B Lee; Charles J Simmons; Yuk-Ching Tse-Dinh; Julian G Hurdle; Richard E Lee; Dianqing Sun Journal: J Med Chem Date: 2014-10-07 Impact factor: 7.446
Authors: Philip T Cherian; Xiaoqian Wu; Marcus M Maddox; Aman P Singh; Richard E Lee; Julian G Hurdle Journal: Sci Rep Date: 2014-04-17 Impact factor: 4.379