Thiosemicarbazones as inhibitors of tyrosinase enzyme
[Display omitted] In the search for compounds which may inhibit the development of melanomas, a series of thiosemicarbazones has been investigated as possible inhibitors of the tyrosinase enzyme. The results showed that all the thiosemicarbazones tested exhibited significant inhibitory effects on th...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2017-08, Vol.27 (15), p.3546-3550 |
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| creator | Soares, Mariana A. Almeida, Mariana A. Marins-Goulart, Carla Chaves, Otávio A. Echevarria, Aurea de Oliveira, Márcia C.C. |
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In the search for compounds which may inhibit the development of melanomas, a series of thiosemicarbazones has been investigated as possible inhibitors of the tyrosinase enzyme. The results showed that all the thiosemicarbazones tested exhibited significant inhibitory effects on the enzyme. Thiosemicarbazones Thio-1, Thio-2, Thio-3 and Thio-4 substituted with oxygenate moieties, were better inhibitors (IC50 0.42, 0.35, 0.36 and 0.44mM, respectively) than Thio-5, Thio-6, Thio-7 and Thio-8. For the better inhibitors, molecular docking results suggested that the oxygen present in the para position of the aromatic ring is essential for the tyrosinase inhibition, due its high ability for complexation with Cu2+ ions. Inside the active protein pocket, Thio-2 – the best studied inhibitor – is able to interact with the amino acid residues His-155, Gly-170 and Val-172 via hydrogen bonding and hydrophobic force. Thio-2, containing a substituent on the aromatic ring similar to the substrate l-DOPA, showed a competitive inhibition mechanism as viewed in a Lineweaver–Burk plot. The same results were observed in the UV–Vis curves. |
| doi_str_mv | 10.1016/j.bmcl.2017.05.057 |
| format | Article |
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In the search for compounds which may inhibit the development of melanomas, a series of thiosemicarbazones has been investigated as possible inhibitors of the tyrosinase enzyme. The results showed that all the thiosemicarbazones tested exhibited significant inhibitory effects on the enzyme. Thiosemicarbazones Thio-1, Thio-2, Thio-3 and Thio-4 substituted with oxygenate moieties, were better inhibitors (IC50 0.42, 0.35, 0.36 and 0.44mM, respectively) than Thio-5, Thio-6, Thio-7 and Thio-8. For the better inhibitors, molecular docking results suggested that the oxygen present in the para position of the aromatic ring is essential for the tyrosinase inhibition, due its high ability for complexation with Cu2+ ions. Inside the active protein pocket, Thio-2 – the best studied inhibitor – is able to interact with the amino acid residues His-155, Gly-170 and Val-172 via hydrogen bonding and hydrophobic force. Thio-2, containing a substituent on the aromatic ring similar to the substrate l-DOPA, showed a competitive inhibition mechanism as viewed in a Lineweaver–Burk plot. The same results were observed in the UV–Vis curves.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2017.05.057</identifier><identifier>PMID: 28583798</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Agaricales - drug effects ; Agaricales - enzymology ; Enzyme Inhibitors - chemistry ; Enzyme Inhibitors - pharmacology ; Humans ; Levodopa - metabolism ; Melanin ; Melanins - metabolism ; Melanoma - drug therapy ; Melanoma - enzymology ; Melanome ; Molecular docking ; Molecular Docking Simulation ; Monophenol Monooxygenase - antagonists & inhibitors ; Monophenol Monooxygenase - metabolism ; Phenol oxidase ; Thiosemicarbazones ; Thiosemicarbazones - chemistry ; Thiosemicarbazones - pharmacology</subject><ispartof>Bioorganic & medicinal chemistry letters, 2017-08, Vol.27 (15), p.3546-3550</ispartof><rights>2017 Elsevier Ltd</rights><rights>Copyright © 2017 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-5d92cdf43bf54485e0a35203cecf79f29da3b3e2800c2dbede66b51cc9864e073</citedby><cites>FETCH-LOGICAL-c356t-5d92cdf43bf54485e0a35203cecf79f29da3b3e2800c2dbede66b51cc9864e073</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bmcl.2017.05.057$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28583798$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Soares, Mariana A.</creatorcontrib><creatorcontrib>Almeida, Mariana A.</creatorcontrib><creatorcontrib>Marins-Goulart, Carla</creatorcontrib><creatorcontrib>Chaves, Otávio A.</creatorcontrib><creatorcontrib>Echevarria, Aurea</creatorcontrib><creatorcontrib>de Oliveira, Márcia C.C.</creatorcontrib><title>Thiosemicarbazones as inhibitors of tyrosinase enzyme</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>[Display omitted]
In the search for compounds which may inhibit the development of melanomas, a series of thiosemicarbazones has been investigated as possible inhibitors of the tyrosinase enzyme. The results showed that all the thiosemicarbazones tested exhibited significant inhibitory effects on the enzyme. Thiosemicarbazones Thio-1, Thio-2, Thio-3 and Thio-4 substituted with oxygenate moieties, were better inhibitors (IC50 0.42, 0.35, 0.36 and 0.44mM, respectively) than Thio-5, Thio-6, Thio-7 and Thio-8. For the better inhibitors, molecular docking results suggested that the oxygen present in the para position of the aromatic ring is essential for the tyrosinase inhibition, due its high ability for complexation with Cu2+ ions. Inside the active protein pocket, Thio-2 – the best studied inhibitor – is able to interact with the amino acid residues His-155, Gly-170 and Val-172 via hydrogen bonding and hydrophobic force. Thio-2, containing a substituent on the aromatic ring similar to the substrate l-DOPA, showed a competitive inhibition mechanism as viewed in a Lineweaver–Burk plot. The same results were observed in the UV–Vis curves.</description><subject>Agaricales - drug effects</subject><subject>Agaricales - enzymology</subject><subject>Enzyme Inhibitors - chemistry</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Humans</subject><subject>Levodopa - metabolism</subject><subject>Melanin</subject><subject>Melanins - metabolism</subject><subject>Melanoma - drug therapy</subject><subject>Melanoma - enzymology</subject><subject>Melanome</subject><subject>Molecular docking</subject><subject>Molecular Docking Simulation</subject><subject>Monophenol Monooxygenase - antagonists & inhibitors</subject><subject>Monophenol Monooxygenase - metabolism</subject><subject>Phenol oxidase</subject><subject>Thiosemicarbazones</subject><subject>Thiosemicarbazones - chemistry</subject><subject>Thiosemicarbazones - pharmacology</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1Lw0AQhhdRbK3-AQ-So5fE2a8kC15E_IKClwrelt3NhG5pkrqbCu2vN6HVo_DCXJ55mHkJuaaQUaD53SqzjVtnDGiRgRxSnJApFblIuQB5SqagckhLJT4n5CLGFQAVIMQ5mbBSlrxQ5ZTIxdJ3ERvvTLBm37UYExMT3y699X0XYtLVSb8LXfStiZhgu981eEnOarOOeHWcM_Lx_LR4fE3n7y9vjw_z1HGZ96msFHNVLbitpRClRDBcMuAOXV2omqnKcMuRlQCOVRYrzHMrqXOqzAVCwWfk9uDdhO5ri7HXjY8O12vTYreNmirIRUGZUgPKDqgbbo0Ba70JvjFhpynosS690mNdeqxLgxwy-m-O_q1tsPpb-e1nAO4PAA5ffnsMOjqPrcPKB3S9rjr_n_8HgT98PA</recordid><startdate>20170801</startdate><enddate>20170801</enddate><creator>Soares, Mariana A.</creator><creator>Almeida, Mariana A.</creator><creator>Marins-Goulart, Carla</creator><creator>Chaves, Otávio A.</creator><creator>Echevarria, Aurea</creator><creator>de Oliveira, Márcia C.C.</creator><general>Elsevier Ltd</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>20170801</creationdate><title>Thiosemicarbazones as inhibitors of tyrosinase enzyme</title><author>Soares, Mariana A. ; Almeida, Mariana A. ; Marins-Goulart, Carla ; Chaves, Otávio A. ; Echevarria, Aurea ; de Oliveira, Márcia C.C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-5d92cdf43bf54485e0a35203cecf79f29da3b3e2800c2dbede66b51cc9864e073</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Agaricales - drug effects</topic><topic>Agaricales - enzymology</topic><topic>Enzyme Inhibitors - chemistry</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Humans</topic><topic>Levodopa - metabolism</topic><topic>Melanin</topic><topic>Melanins - metabolism</topic><topic>Melanoma - drug therapy</topic><topic>Melanoma - enzymology</topic><topic>Melanome</topic><topic>Molecular docking</topic><topic>Molecular Docking Simulation</topic><topic>Monophenol Monooxygenase - antagonists & inhibitors</topic><topic>Monophenol Monooxygenase - metabolism</topic><topic>Phenol oxidase</topic><topic>Thiosemicarbazones</topic><topic>Thiosemicarbazones - chemistry</topic><topic>Thiosemicarbazones - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Soares, Mariana A.</creatorcontrib><creatorcontrib>Almeida, Mariana A.</creatorcontrib><creatorcontrib>Marins-Goulart, Carla</creatorcontrib><creatorcontrib>Chaves, Otávio A.</creatorcontrib><creatorcontrib>Echevarria, Aurea</creatorcontrib><creatorcontrib>de Oliveira, Márcia C.C.</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 & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Soares, Mariana A.</au><au>Almeida, Mariana A.</au><au>Marins-Goulart, Carla</au><au>Chaves, Otávio A.</au><au>Echevarria, Aurea</au><au>de Oliveira, Márcia C.C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Thiosemicarbazones as inhibitors of tyrosinase enzyme</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2017-08-01</date><risdate>2017</risdate><volume>27</volume><issue>15</issue><spage>3546</spage><epage>3550</epage><pages>3546-3550</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>[Display omitted]
In the search for compounds which may inhibit the development of melanomas, a series of thiosemicarbazones has been investigated as possible inhibitors of the tyrosinase enzyme. The results showed that all the thiosemicarbazones tested exhibited significant inhibitory effects on the enzyme. Thiosemicarbazones Thio-1, Thio-2, Thio-3 and Thio-4 substituted with oxygenate moieties, were better inhibitors (IC50 0.42, 0.35, 0.36 and 0.44mM, respectively) than Thio-5, Thio-6, Thio-7 and Thio-8. For the better inhibitors, molecular docking results suggested that the oxygen present in the para position of the aromatic ring is essential for the tyrosinase inhibition, due its high ability for complexation with Cu2+ ions. Inside the active protein pocket, Thio-2 – the best studied inhibitor – is able to interact with the amino acid residues His-155, Gly-170 and Val-172 via hydrogen bonding and hydrophobic force. Thio-2, containing a substituent on the aromatic ring similar to the substrate l-DOPA, showed a competitive inhibition mechanism as viewed in a Lineweaver–Burk plot. The same results were observed in the UV–Vis curves.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>28583798</pmid><doi>10.1016/j.bmcl.2017.05.057</doi><tpages>5</tpages></addata></record> |
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| subjects | Agaricales - drug effects Agaricales - enzymology Enzyme Inhibitors - chemistry Enzyme Inhibitors - pharmacology Humans Levodopa - metabolism Melanin Melanins - metabolism Melanoma - drug therapy Melanoma - enzymology Melanome Molecular docking Molecular Docking Simulation Monophenol Monooxygenase - antagonists & inhibitors Monophenol Monooxygenase - metabolism Phenol oxidase Thiosemicarbazones Thiosemicarbazones - chemistry Thiosemicarbazones - pharmacology |
| title | Thiosemicarbazones as inhibitors of tyrosinase enzyme |
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