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Flavonoids: True or promiscuous inhibitors of enzyme? The case of deoxyxylulose phosphate reductoisomerase
[Display omitted] •Possible erroneous conclusions regarding the inhibition of enzymes by flavonoids.•Hydrophobic molecules can generate aggregates responsible of enzyme inhibition.•Inhibition studies with flavonoids require additional testing with non-ionic detergent.•Flavonoids inhibit deoxyxylulos...
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Published in: | Bioorganic chemistry 2015-04, Vol.59, p.140-144 |
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container_title | Bioorganic chemistry |
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creator | Tritsch, Denis Zinglé, Catherine Rohmer, Michel Grosdemange-Billiard, Catherine |
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•Possible erroneous conclusions regarding the inhibition of enzymes by flavonoids.•Hydrophobic molecules can generate aggregates responsible of enzyme inhibition.•Inhibition studies with flavonoids require additional testing with non-ionic detergent.•Flavonoids inhibit deoxyxylulose phosphate reductoisomerase via a non-specific way.
Flavonoids, due to their physical and chemical properties (among them hydrophobicity and metal chelation abilities), are potential inhibitors of the 1-deoxyxylulose 5-phosphate reductoisomerase and most of the tested flavonoids effectively inhibited its activity with encouraging IC50 values in the micromolar range. The addition of 0.01% Triton X100 in the assays led however, to a dramatic decrease of the inhibition revealing that a non-specific inhibition probably takes place. Our study highlights the possibility of erroneous conclusions regarding the inhibition of enzymes by flavonoids that are able to produce aggregates in micromolar range. Therefore, the addition of a detergent in the assays prevents possible false positive hits in high throughput screenings. |
doi_str_mv | 10.1016/j.bioorg.2015.02.008 |
format | article |
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•Possible erroneous conclusions regarding the inhibition of enzymes by flavonoids.•Hydrophobic molecules can generate aggregates responsible of enzyme inhibition.•Inhibition studies with flavonoids require additional testing with non-ionic detergent.•Flavonoids inhibit deoxyxylulose phosphate reductoisomerase via a non-specific way.
Flavonoids, due to their physical and chemical properties (among them hydrophobicity and metal chelation abilities), are potential inhibitors of the 1-deoxyxylulose 5-phosphate reductoisomerase and most of the tested flavonoids effectively inhibited its activity with encouraging IC50 values in the micromolar range. The addition of 0.01% Triton X100 in the assays led however, to a dramatic decrease of the inhibition revealing that a non-specific inhibition probably takes place. Our study highlights the possibility of erroneous conclusions regarding the inhibition of enzymes by flavonoids that are able to produce aggregates in micromolar range. Therefore, the addition of a detergent in the assays prevents possible false positive hits in high throughput screenings.</description><identifier>ISSN: 0045-2068</identifier><identifier>EISSN: 1090-2120</identifier><identifier>DOI: 10.1016/j.bioorg.2015.02.008</identifier><identifier>PMID: 25800132</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>1-Deoxyxylulose 5-phosphate reductoisomerase ; 2-C-methyl-D-erythritol 4-phosphate pathway ; Aldose-Ketose Isomerases - antagonists & inhibitors ; Aldose-Ketose Isomerases - metabolism ; Enzyme Inhibitors - chemistry ; Enzyme Inhibitors - pharmacology ; Escherichia coli - drug effects ; Escherichia coli - enzymology ; Escherichia coli Infections - microbiology ; Flavonoids ; Flavonoids - chemistry ; Flavonoids - pharmacology ; Humans ; Promiscuous inhibition</subject><ispartof>Bioorganic chemistry, 2015-04, Vol.59, p.140-144</ispartof><rights>2015 Elsevier Inc.</rights><rights>Copyright © 2015 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c362t-e879422d2dc2ed4f827069251800acfe73541bf470f0abfd9d0dc5a57591495b3</citedby><cites>FETCH-LOGICAL-c362t-e879422d2dc2ed4f827069251800acfe73541bf470f0abfd9d0dc5a57591495b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25800132$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tritsch, Denis</creatorcontrib><creatorcontrib>Zinglé, Catherine</creatorcontrib><creatorcontrib>Rohmer, Michel</creatorcontrib><creatorcontrib>Grosdemange-Billiard, Catherine</creatorcontrib><title>Flavonoids: True or promiscuous inhibitors of enzyme? The case of deoxyxylulose phosphate reductoisomerase</title><title>Bioorganic chemistry</title><addtitle>Bioorg Chem</addtitle><description>[Display omitted]
•Possible erroneous conclusions regarding the inhibition of enzymes by flavonoids.•Hydrophobic molecules can generate aggregates responsible of enzyme inhibition.•Inhibition studies with flavonoids require additional testing with non-ionic detergent.•Flavonoids inhibit deoxyxylulose phosphate reductoisomerase via a non-specific way.
Flavonoids, due to their physical and chemical properties (among them hydrophobicity and metal chelation abilities), are potential inhibitors of the 1-deoxyxylulose 5-phosphate reductoisomerase and most of the tested flavonoids effectively inhibited its activity with encouraging IC50 values in the micromolar range. The addition of 0.01% Triton X100 in the assays led however, to a dramatic decrease of the inhibition revealing that a non-specific inhibition probably takes place. Our study highlights the possibility of erroneous conclusions regarding the inhibition of enzymes by flavonoids that are able to produce aggregates in micromolar range. Therefore, the addition of a detergent in the assays prevents possible false positive hits in high throughput screenings.</description><subject>1-Deoxyxylulose 5-phosphate reductoisomerase</subject><subject>2-C-methyl-D-erythritol 4-phosphate pathway</subject><subject>Aldose-Ketose Isomerases - antagonists & inhibitors</subject><subject>Aldose-Ketose Isomerases - metabolism</subject><subject>Enzyme Inhibitors - chemistry</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Escherichia coli - drug effects</subject><subject>Escherichia coli - enzymology</subject><subject>Escherichia coli Infections - microbiology</subject><subject>Flavonoids</subject><subject>Flavonoids - chemistry</subject><subject>Flavonoids - pharmacology</subject><subject>Humans</subject><subject>Promiscuous inhibition</subject><issn>0045-2068</issn><issn>1090-2120</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNp9kE1v1DAQhi1URJfCP0DIx14SxrN2PjhQVRUFpEpclrPl2BPWqyRe7KTq9tfj1bY99jTy6JkZvw9jnwSUAkT1ZVd2PoT4t0QQqgQsAZo3bCWghQIFwhlbAUhVIFTNOXuf0g5ACFlX79g5qiY_1rhiu9vB3IcpeJe-8k1ciIfI9zGMPtklLIn7aes7P4eYeOg5TY-Hka74ZkvcmkTHnqPwcHg4DMsQcmO_DWm_NTPxSG6xc_ApjBQz-4G97c2Q6ONTvWB_br9vbn4Wd79__Lq5vivsusK5oKZuJaJDZ5Gc7BusoWpRifxlY3uq10qKrpc19GC63rUOnFVG1aoVslXd-oJdnvbmGP8WSrM-hqFhMBPlRFpUNUJTS8CMyhNqY0gpUq_30Y8mHrQAfbSsd_pkWR8ta0CdLeexz08Xlm4k9zL0rDUD304A5Zz3nqJO1tNkyflIdtYu-Ncv_AfeI5G-</recordid><startdate>20150401</startdate><enddate>20150401</enddate><creator>Tritsch, Denis</creator><creator>Zinglé, Catherine</creator><creator>Rohmer, Michel</creator><creator>Grosdemange-Billiard, Catherine</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20150401</creationdate><title>Flavonoids: True or promiscuous inhibitors of enzyme? The case of deoxyxylulose phosphate reductoisomerase</title><author>Tritsch, Denis ; Zinglé, Catherine ; Rohmer, Michel ; Grosdemange-Billiard, Catherine</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c362t-e879422d2dc2ed4f827069251800acfe73541bf470f0abfd9d0dc5a57591495b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>1-Deoxyxylulose 5-phosphate reductoisomerase</topic><topic>2-C-methyl-D-erythritol 4-phosphate pathway</topic><topic>Aldose-Ketose Isomerases - antagonists & inhibitors</topic><topic>Aldose-Ketose Isomerases - metabolism</topic><topic>Enzyme Inhibitors - chemistry</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Escherichia coli - drug effects</topic><topic>Escherichia coli - enzymology</topic><topic>Escherichia coli Infections - microbiology</topic><topic>Flavonoids</topic><topic>Flavonoids - chemistry</topic><topic>Flavonoids - pharmacology</topic><topic>Humans</topic><topic>Promiscuous inhibition</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tritsch, Denis</creatorcontrib><creatorcontrib>Zinglé, Catherine</creatorcontrib><creatorcontrib>Rohmer, Michel</creatorcontrib><creatorcontrib>Grosdemange-Billiard, Catherine</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Bioorganic chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tritsch, Denis</au><au>Zinglé, Catherine</au><au>Rohmer, Michel</au><au>Grosdemange-Billiard, Catherine</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Flavonoids: True or promiscuous inhibitors of enzyme? The case of deoxyxylulose phosphate reductoisomerase</atitle><jtitle>Bioorganic chemistry</jtitle><addtitle>Bioorg Chem</addtitle><date>2015-04-01</date><risdate>2015</risdate><volume>59</volume><spage>140</spage><epage>144</epage><pages>140-144</pages><issn>0045-2068</issn><eissn>1090-2120</eissn><abstract>[Display omitted]
•Possible erroneous conclusions regarding the inhibition of enzymes by flavonoids.•Hydrophobic molecules can generate aggregates responsible of enzyme inhibition.•Inhibition studies with flavonoids require additional testing with non-ionic detergent.•Flavonoids inhibit deoxyxylulose phosphate reductoisomerase via a non-specific way.
Flavonoids, due to their physical and chemical properties (among them hydrophobicity and metal chelation abilities), are potential inhibitors of the 1-deoxyxylulose 5-phosphate reductoisomerase and most of the tested flavonoids effectively inhibited its activity with encouraging IC50 values in the micromolar range. The addition of 0.01% Triton X100 in the assays led however, to a dramatic decrease of the inhibition revealing that a non-specific inhibition probably takes place. Our study highlights the possibility of erroneous conclusions regarding the inhibition of enzymes by flavonoids that are able to produce aggregates in micromolar range. Therefore, the addition of a detergent in the assays prevents possible false positive hits in high throughput screenings.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>25800132</pmid><doi>10.1016/j.bioorg.2015.02.008</doi><tpages>5</tpages></addata></record> |
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subjects | 1-Deoxyxylulose 5-phosphate reductoisomerase 2-C-methyl-D-erythritol 4-phosphate pathway Aldose-Ketose Isomerases - antagonists & inhibitors Aldose-Ketose Isomerases - metabolism Enzyme Inhibitors - chemistry Enzyme Inhibitors - pharmacology Escherichia coli - drug effects Escherichia coli - enzymology Escherichia coli Infections - microbiology Flavonoids Flavonoids - chemistry Flavonoids - pharmacology Humans Promiscuous inhibition |
title | Flavonoids: True or promiscuous inhibitors of enzyme? The case of deoxyxylulose phosphate reductoisomerase |
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