Antibacterial and antifungal activities of new acylated derivatives of epigallocatechin gallate.
Antibacterial and antifungal activities of new acylated derivatives of epigallocatechin gallate.
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DOI：
10.3389/fmicb.2012.00053
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发表时间：
2012
影响因子：
5.2
通讯作者：
Yamaguchi A
中科院分区：
文献类型：
--
作者：
Matsumoto Y;Kaihatsu K;Nishino K;Ogawa M;Kato N;Yamaguchi A
（−）-表没食子儿茶素-3- o -没食子酸酯（EGCG）具有有用的抗病毒、抗菌、抗毒素和抗肿瘤特性。此前，Mori等人发现，在EGCG中添加长酰基链（C16-18）可使其抗流感病毒活性提高44倍。酰化也增强了EGCG抗氧化降解的化学稳定性。我们进一步评估了EGCG衍生物对多种细菌和真菌的体外活性谱。采用脂肪酶催化酯交换法合成了一系列EGCG o -酰基衍生物。这些衍生物表现出比EGCG高几倍的活性，特别是对革兰氏阳性生物。其衍生物的抗真菌mic值也比EGCG低2 ~ 4倍。EGCG衍生物对革兰氏阴性菌的抑菌活性与EGCG没有明显区别。在所评价的衍生物中，重辛酸酯和棕榈酸酯（C16）对17株金黄色葡萄球菌的MIC为4 ~ 32 μg/ml，而EGCG对17株金黄色葡萄球菌的MIC均≥128 μg/ml。在≥16 μg/ml浓度下，C16对耐甲氧西林金黄色葡萄球菌（MRSA） ATCC43300具有快速杀菌活性。C16抗金黄色葡萄球菌活性的增强是通过SYTOX Green摄取增加来测定其膜渗透活性的增强。EGCG衍生物通过acrabb - tolc外排泵在大肠杆菌中输出。tolC缺失突变体对EGCG及其衍生物的敏感性高于野生型。在EGCG中加入长烷基链可显著增强其对多种细菌和真菌的活性，尤其是对金黄色葡萄球菌（包括MRSA）的活性。C16将来可能在特定情况下成为抗生素和消毒剂的替代品或补充物。
(−)-Epigallocatechin-3-O-gallate (EGCG) has useful antiviral, antimicrobial, antitoxin, and antitumor properties. Previously, Mori et al. found that addition of long acyl chains (C16–18) to EGCG enhanced its anti-influenza virus activity up to 44-fold. The chemical stability of EGCG against oxidative degradation was also enhanced by acylation. We further evaluated the in vitro activity spectrum of the EGCG derivatives against a wide range of bacteria and fungi. A series of EGCG O-acyl derivatives were synthesized by lipase-catalyzed transesterification. These derivatives exhibited several-fold higher activities than EGCG, particularly against Gram-positive organisms. Antifungal MICs of the derivatives were also two to fourfold lower than those of EGCG. The activities of the EGCG derivatives against Gram-negative bacteria were not distinguishable from those of EGCG. Among the derivatives evaluated, MICs of dioctanoate and palmitate (C16) for 17 Staphylococcus aureus strains were 4–32 μg/ml, although MIC of EGCG for these 17 strains was ≥128 μg/ml. C16 demonstrated rapid bactericidal activity against methicillin-resistant S. aureus (MRSA) ATCC43300 at ≥16 μg/ml. The enhanced activity of C16 against S. aureus was supported by its increased membrane-permeabilizing activity determined by increased SYTOX Green uptake. The EGCG derivatives were exported in Escherichia coli using the efflux pump AcrAB–TolC. The tolC deletion mutant exhibited higher sensitivity to EGCG and the derivatives than wild-type. Addition of long alkyl chains to EGCG significantly enhanced its activities against several bacteria and fungi, particularly against S. aureus including MRSA. C16 might potentially become under specified circumstances an alternative or supplement to antibiotics and disinfectants in the future.
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影响因子：
2
作者：
Kajiya, Katsuko;Kumazawa, Shigenori;Nakayama, Tsutomu
通讯作者：
Nakayama, Tsutomu
影响因子：
1.6
作者：
Kumazawa, S;Kajiya, K;Nakayama, T
通讯作者：
Nakayama, T
影响因子：
2.7
作者：
Mori, Shuichi;Miyake, Shinya;Kaihatsu, Kunihiro
通讯作者：
Kaihatsu, Kunihiro
影响因子：
1.6
作者：
Kamihira，Miya;Nakazawa，Hiromi;Nakayama，Tsutomu
通讯作者：
Nakayama，Tsutomu
影响因子：
7.6
作者：
NAKAYAMA, M;SUZUKI, K;SHIMAMURA, T
通讯作者：
SHIMAMURA, T