Design and discovery of tyrosinase inhibitors based on a coumarin scaffold
In this manuscript we report the synthesis, pharmacological evaluation and docking studies of a selected series of 3-aryl and 3-heteroarylcoumarins with the aim of finding structural features for the tyrosinase inhibitory activity. The synthesized compounds were evaluated as mushroom tyrosinase inhi...
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Veröffentlicht in: | RSC advances 2015-01, Vol.5 (114), p.94227-94235 |
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creator | Matos, M. J. Varela, C. Vilar, S. Hripcsak, G. Borges, F. Santana, L. Uriarte, E. Fais, A. Di Petrillo, A. Pintus, F. Era, B. |
description | In this manuscript we report the synthesis, pharmacological evaluation and docking studies of a selected series of 3-aryl and 3-heteroarylcoumarins with the aim of finding structural features for the tyrosinase inhibitory activity. The synthesized compounds were evaluated as mushroom tyrosinase inhibitors. Compound
12b
showed the lowest IC
50
(0.19 μM) of the series, being approximately 100 times more active than kojic acid, used as a reference compound. The kinetic studies of tyrosinase inhibition revealed that
12b
acts as a competitive inhibitor of mushroom tyrosinase with
l
-DOPA as the substrate. Furthermore, the absence of cytotoxicity in B16F10 melanoma cells was determined for this compound. The antioxidant profile of all the derivatives was evaluated by measuring radical scavenging capacity (ABTS and DPPH assays). Docking experiments were carried out on mushroom tyrosinase structures to better understand the structure–activity relationships. |
doi_str_mv | 10.1039/C5RA14465E |
format | Article |
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12b
showed the lowest IC
50
(0.19 μM) of the series, being approximately 100 times more active than kojic acid, used as a reference compound. The kinetic studies of tyrosinase inhibition revealed that
12b
acts as a competitive inhibitor of mushroom tyrosinase with
l
-DOPA as the substrate. Furthermore, the absence of cytotoxicity in B16F10 melanoma cells was determined for this compound. The antioxidant profile of all the derivatives was evaluated by measuring radical scavenging capacity (ABTS and DPPH assays). Docking experiments were carried out on mushroom tyrosinase structures to better understand the structure–activity relationships.</description><identifier>ISSN: 2046-2069</identifier><identifier>EISSN: 2046-2069</identifier><identifier>DOI: 10.1039/C5RA14465E</identifier><language>eng</language><subject>Derivatives ; Docking ; Inhibitors ; Mushrooms ; Pharmacology ; Radicals ; Scavenging ; Tyrosinase</subject><ispartof>RSC advances, 2015-01, Vol.5 (114), p.94227-94235</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c300t-e4c82d70a275c5d15ee5fe83a8b1278a2cb69d8b3d035b4d3a68eb006f903ae23</citedby><cites>FETCH-LOGICAL-c300t-e4c82d70a275c5d15ee5fe83a8b1278a2cb69d8b3d035b4d3a68eb006f903ae23</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></links><search><creatorcontrib>Matos, M. J.</creatorcontrib><creatorcontrib>Varela, C.</creatorcontrib><creatorcontrib>Vilar, S.</creatorcontrib><creatorcontrib>Hripcsak, G.</creatorcontrib><creatorcontrib>Borges, F.</creatorcontrib><creatorcontrib>Santana, L.</creatorcontrib><creatorcontrib>Uriarte, E.</creatorcontrib><creatorcontrib>Fais, A.</creatorcontrib><creatorcontrib>Di Petrillo, A.</creatorcontrib><creatorcontrib>Pintus, F.</creatorcontrib><creatorcontrib>Era, B.</creatorcontrib><title>Design and discovery of tyrosinase inhibitors based on a coumarin scaffold</title><title>RSC advances</title><description>In this manuscript we report the synthesis, pharmacological evaluation and docking studies of a selected series of 3-aryl and 3-heteroarylcoumarins with the aim of finding structural features for the tyrosinase inhibitory activity. The synthesized compounds were evaluated as mushroom tyrosinase inhibitors. Compound
12b
showed the lowest IC
50
(0.19 μM) of the series, being approximately 100 times more active than kojic acid, used as a reference compound. The kinetic studies of tyrosinase inhibition revealed that
12b
acts as a competitive inhibitor of mushroom tyrosinase with
l
-DOPA as the substrate. Furthermore, the absence of cytotoxicity in B16F10 melanoma cells was determined for this compound. The antioxidant profile of all the derivatives was evaluated by measuring radical scavenging capacity (ABTS and DPPH assays). Docking experiments were carried out on mushroom tyrosinase structures to better understand the structure–activity relationships.</description><subject>Derivatives</subject><subject>Docking</subject><subject>Inhibitors</subject><subject>Mushrooms</subject><subject>Pharmacology</subject><subject>Radicals</subject><subject>Scavenging</subject><subject>Tyrosinase</subject><issn>2046-2069</issn><issn>2046-2069</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNpNkFtLAzEQhYMoWGpf_AV5FGE1l002-1hqvVEQRJ-XXCYa2W5qshX23xupoMPAnIHD8M1B6JySK0p4e70Sz0ta11Ksj9CMkVpWjMj2-J8-RYucP0gpKSiTdIYebyCHtwHrwWEXso1fkCYcPR6nFHMYdAYchvdgwhhTxqbsDsfixzbutzqFAWervY-9O0MnXvcZFr9zjl5v1y-r-2rzdPewWm4qywkZK6itYq4hmjXCCkcFgPCguFaGskZpZo1snTLcES5M7biWCkwh9i3hGhifo4vD3V2Kn3vIY7ct4ND3eoC4zx1VXEhSWhbr5cFqyzM5ge92KRTqqaOk-8ms-8uMfwM4Y15N</recordid><startdate>20150101</startdate><enddate>20150101</enddate><creator>Matos, M. J.</creator><creator>Varela, C.</creator><creator>Vilar, S.</creator><creator>Hripcsak, G.</creator><creator>Borges, F.</creator><creator>Santana, L.</creator><creator>Uriarte, E.</creator><creator>Fais, A.</creator><creator>Di Petrillo, A.</creator><creator>Pintus, F.</creator><creator>Era, B.</creator><scope>AAYXX</scope><scope>CITATION</scope><scope>7SR</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope></search><sort><creationdate>20150101</creationdate><title>Design and discovery of tyrosinase inhibitors based on a coumarin scaffold</title><author>Matos, M. J. ; Varela, C. ; Vilar, S. ; Hripcsak, G. ; Borges, F. ; Santana, L. ; Uriarte, E. ; Fais, A. ; Di Petrillo, A. ; Pintus, F. ; Era, B.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c300t-e4c82d70a275c5d15ee5fe83a8b1278a2cb69d8b3d035b4d3a68eb006f903ae23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Derivatives</topic><topic>Docking</topic><topic>Inhibitors</topic><topic>Mushrooms</topic><topic>Pharmacology</topic><topic>Radicals</topic><topic>Scavenging</topic><topic>Tyrosinase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Matos, M. J.</creatorcontrib><creatorcontrib>Varela, C.</creatorcontrib><creatorcontrib>Vilar, S.</creatorcontrib><creatorcontrib>Hripcsak, G.</creatorcontrib><creatorcontrib>Borges, F.</creatorcontrib><creatorcontrib>Santana, L.</creatorcontrib><creatorcontrib>Uriarte, E.</creatorcontrib><creatorcontrib>Fais, A.</creatorcontrib><creatorcontrib>Di Petrillo, A.</creatorcontrib><creatorcontrib>Pintus, F.</creatorcontrib><creatorcontrib>Era, B.</creatorcontrib><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><jtitle>RSC advances</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Matos, M. J.</au><au>Varela, C.</au><au>Vilar, S.</au><au>Hripcsak, G.</au><au>Borges, F.</au><au>Santana, L.</au><au>Uriarte, E.</au><au>Fais, A.</au><au>Di Petrillo, A.</au><au>Pintus, F.</au><au>Era, B.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Design and discovery of tyrosinase inhibitors based on a coumarin scaffold</atitle><jtitle>RSC advances</jtitle><date>2015-01-01</date><risdate>2015</risdate><volume>5</volume><issue>114</issue><spage>94227</spage><epage>94235</epage><pages>94227-94235</pages><issn>2046-2069</issn><eissn>2046-2069</eissn><abstract>In this manuscript we report the synthesis, pharmacological evaluation and docking studies of a selected series of 3-aryl and 3-heteroarylcoumarins with the aim of finding structural features for the tyrosinase inhibitory activity. The synthesized compounds were evaluated as mushroom tyrosinase inhibitors. Compound
12b
showed the lowest IC
50
(0.19 μM) of the series, being approximately 100 times more active than kojic acid, used as a reference compound. The kinetic studies of tyrosinase inhibition revealed that
12b
acts as a competitive inhibitor of mushroom tyrosinase with
l
-DOPA as the substrate. Furthermore, the absence of cytotoxicity in B16F10 melanoma cells was determined for this compound. The antioxidant profile of all the derivatives was evaluated by measuring radical scavenging capacity (ABTS and DPPH assays). Docking experiments were carried out on mushroom tyrosinase structures to better understand the structure–activity relationships.</abstract><doi>10.1039/C5RA14465E</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Derivatives Docking Inhibitors Mushrooms Pharmacology Radicals Scavenging Tyrosinase |
title | Design and discovery of tyrosinase inhibitors based on a coumarin scaffold |
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