Antibacterial and antifungal activities of new acylated derivatives of epigallocatechin gallate
(-)-Epigallocatechin-3-O-gallate (EGCG) has useful antiviral, antimicrobial, antitoxin, and antitumor properties. Previously, Mori, S. et al. (Bioorg Med Chem Lett 18:4249-4252, 2008) found that addition of long acyl chains (C16–18) to EGCG enhanced its anti-influenza virus activity up to 44-fold. T...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2012-02-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fmicb.2012.00053/full |
| _version_ | 1818564665732497408 |
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| author | Yoshimi eMatsumoto Kunihiro eKaihatsu Kunihiko eNishino Miho eOgawa Nobuo eKato Akihito eYamaguchi Akihito eYamaguchi |
| author_facet | Yoshimi eMatsumoto Kunihiro eKaihatsu Kunihiko eNishino Miho eOgawa Nobuo eKato Akihito eYamaguchi Akihito eYamaguchi |
| author_sort | Yoshimi eMatsumoto |
| collection | DOAJ |
| description | (-)-Epigallocatechin-3-O-gallate (EGCG) has useful antiviral, antimicrobial, antitoxin, and antitumor properties. Previously, Mori, S. et al. (Bioorg Med Chem Lett 18:4249-4252, 2008) 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 activities of the derivatives were also 2 to 4-fold superior to 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, palmitate (C16), palmitoleate, and linolenate 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 MRSA at 25 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 by the efflux pump AcrAB-TolC of Escherichia coli. The tolC deletion mutant exhibited higher sensitivity to C16 than to EGCG. Addition of long alkyl chains to EGCG significantly enhanced its activities against various bacteria and fungi, particularly against S. aureus including MRSA. C16 would be an alternative to antibiotics and disinfectants. |
| first_indexed | 2024-12-14T01:31:40Z |
| format | Article |
| id | doaj.art-7d92bab5c9f746649dc9d4b656f0fd42 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-14T01:31:40Z |
| publishDate | 2012-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-7d92bab5c9f746649dc9d4b656f0fd422022-12-21T23:22:02ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2012-02-01310.3389/fmicb.2012.0005317445Antibacterial and antifungal activities of new acylated derivatives of epigallocatechin gallateYoshimi eMatsumoto0Kunihiro eKaihatsu1Kunihiko eNishino2Miho eOgawa3Nobuo eKato4Akihito eYamaguchi5Akihito eYamaguchi6Osaka UniversityOsaka UniversityOsaka UniversityBML, Inc.Osaka UniversityOsaka UniversityOsaka University(-)-Epigallocatechin-3-O-gallate (EGCG) has useful antiviral, antimicrobial, antitoxin, and antitumor properties. Previously, Mori, S. et al. (Bioorg Med Chem Lett 18:4249-4252, 2008) 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 activities of the derivatives were also 2 to 4-fold superior to 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, palmitate (C16), palmitoleate, and linolenate 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 MRSA at 25 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 by the efflux pump AcrAB-TolC of Escherichia coli. The tolC deletion mutant exhibited higher sensitivity to C16 than to EGCG. Addition of long alkyl chains to EGCG significantly enhanced its activities against various bacteria and fungi, particularly against S. aureus including MRSA. C16 would be an alternative to antibiotics and disinfectants.http://journal.frontiersin.org/Journal/10.3389/fmicb.2012.00053/fullStaphylococcus aureusmode of actionepigallocatechin gallatefatty acid esters |
| spellingShingle | Yoshimi eMatsumoto Kunihiro eKaihatsu Kunihiko eNishino Miho eOgawa Nobuo eKato Akihito eYamaguchi Akihito eYamaguchi Antibacterial and antifungal activities of new acylated derivatives of epigallocatechin gallate Frontiers in Microbiology Staphylococcus aureus mode of action epigallocatechin gallate fatty acid esters |
| title | Antibacterial and antifungal activities of new acylated derivatives of epigallocatechin gallate |
| title_full | Antibacterial and antifungal activities of new acylated derivatives of epigallocatechin gallate |
| title_fullStr | Antibacterial and antifungal activities of new acylated derivatives of epigallocatechin gallate |
| title_full_unstemmed | Antibacterial and antifungal activities of new acylated derivatives of epigallocatechin gallate |
| title_short | Antibacterial and antifungal activities of new acylated derivatives of epigallocatechin gallate |
| title_sort | antibacterial and antifungal activities of new acylated derivatives of epigallocatechin gallate |
| topic | Staphylococcus aureus mode of action epigallocatechin gallate fatty acid esters |
| url | http://journal.frontiersin.org/Journal/10.3389/fmicb.2012.00053/full |
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