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- Paul Dzoyem Jean
- Department of Biochemistry, Faculty of Science, University of Dschang Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo
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- Hamamoto Hiroshi
- Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo
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- Ngameni Barthelemy
- Department of Organic Chemistry, Faculty of Science, University of Yaoundé I
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- Tchaleu Ngadjui Bonaventure
- Department of Organic Chemistry, Faculty of Science, University of Yaoundé I
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- Sekimizu Kazuhisa
- Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo
書誌事項
- タイトル別名
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- Antimicrobial action mechanism of flavonoids from <i>Dorstenia </i>species
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抄録
Naturally occurring flavonoids have been reported to possess antimicrobial activity against a wide range of pathogens. However, the antimicrobial action mechanism of these compounds has not yet been elucidated. This study investigated the mechanism underlying the antibacterial activity of four flavonoids: 6,8-diprenyleriodictyol (1), isobavachalcone (2), 6-prenylapigenin (3) and 4-hydroxylonchocarpin (4). In addition, the toxicity of these compounds was evaluated. Determination of the minimum inhibitory concentrations (MICs) was performed by microbroth dilution method. Radiolabeled thymidine, uridine, and methionine were used to evaluate the effect of the compounds on the biosynthesis of DNA, RNA, and proteins while the sensitive cyanine dye DiS-C3-(5) (3,3'-dipropylthiadicarbocyanine iodide) was used for the effect on membrane potential. Bactericidal/bacteriolysis activities were performed by time-kill kinetic method. In the toxicity study, the numbers of survivors was recorded after injection of compounds into the hemolymph of silkworm larvae. Compounds showed significant antibacterial activity against Staphylococcusaureus including methicillin-resistant S. aureus (MRSA) strains with MICs values ranged between 0.5-128 μg/mL. Depolarization of membrane and inhibition of DNA, RNA, and proteins synthesis were observed in S. aureus when treated with those flavonoids. At 5-fold minimum inhibitory concentration, compounds reduced rapidly the bacterial cell density and caused lysis of S. aureus. Compounds 1, 2, and 4 did not show obvious toxic effects in silkworm larvae up to 625 μg/g of body weight. Flavonoids from Dorstenia species, 6,8-diprenyleriodictyol, isobavachalcone, and 4-hydroxylonchocarpin are bactericidal compounds. They cause damage of cell membrane, leading to the inhibition of macromolecular synthesis. Taking into account the in vivo safety and their significant antimicrobial potency, these flavonoids are promising leads for further drug development.
収録刊行物
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- Drug Discoveries & Therapeutics
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Drug Discoveries & Therapeutics 7 (2), 66-72, 2013
特定非営利活動法人 バイオ＆ソーシャル・サイエンス推進国際研究交流会