Influence of S-Oxidation on Cytotoxic Activity of Oxathiole-Fused Chalcones
Synthesis, in vitro cytotoxic activity, and interaction with tubulin of oxidized, isomeric 1‐(5‐alkoxybenzo[d][1,3]oxathiol‐6‐yl)‐3‐phenylprop‐2‐en‐1‐ones and 1‐(6‐alkoxybenzo[d][1,3]oxathiol‐5‐yl)‐3‐phenylprop‐2‐en‐1‐ones are described. Most of the compounds demonstrated cytotoxic activity at submi...
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| Veröffentlicht in: | Chemical biology & drug design 2016-10, Vol.88 (4), p.519-533 |
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| creator | Konieczny, Marek T. Buɬakowska, Anita Pirska, Danuta Konieczny, Wojciech Skladanowski, Andrzej Sabisz, Michal Wojciechowski, Marek Lemke, Krzysztof |
| description | Synthesis, in vitro cytotoxic activity, and interaction with tubulin of oxidized, isomeric 1‐(5‐alkoxybenzo[d][1,3]oxathiol‐6‐yl)‐3‐phenylprop‐2‐en‐1‐ones and 1‐(6‐alkoxybenzo[d][1,3]oxathiol‐5‐yl)‐3‐phenylprop‐2‐en‐1‐ones are described. Most of the compounds demonstrated cytotoxic activity at submicromolar concentrations. It was found that oxidation of sulfur atom of the oxathiole‐fused chalcones strongly influenced activity of the parent compounds, and that depending on relative position of the sulfur atom in the molecule, the activity was either increased or diminished. For isomers with sulfur atom para to the chalcone carbonyl group, oxidation led to increase in activity, while for isomers with sulfur atom meta to the carbonyl the activity dropped down. It was demonstrated that the compounds interact with tubulin at the colchicine binding site, and the interaction was evaluated using molecular modeling. It was concluded that the observed profound influence of oxidation of the sulfur atom on cytotoxic activity cannot be solely related to interaction of the compounds with tubulin.
Most of the compounds demonstrated cytotoxic activity at submicromolar concentrations. Oxidation of sulfur atom of the oxathiole‐fused chalcones strongly influenced activity of the parent compounds, and depending on relative position of the sulfur atom in the molecule, the activity was either increased or diminished. It was demonstrated that the compounds interact with tubulin at the colchicine binding site. |
| doi_str_mv | 10.1111/cbdd.12776 |
| format | Article |
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Most of the compounds demonstrated cytotoxic activity at submicromolar concentrations. Oxidation of sulfur atom of the oxathiole‐fused chalcones strongly influenced activity of the parent compounds, and depending on relative position of the sulfur atom in the molecule, the activity was either increased or diminished. It was demonstrated that the compounds interact with tubulin at the colchicine binding site.</description><identifier>ISSN: 1747-0277</identifier><identifier>EISSN: 1747-0285</identifier><identifier>DOI: 10.1111/cbdd.12776</identifier><identifier>PMID: 27198732</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>benzoxathiole oxidation ; Cell Line, Tumor ; Cell Survival - drug effects ; chalcone ; Chalcones - chemical synthesis ; Chalcones - chemistry ; Chalcones - toxicity ; cytotoxic activity ; Cytotoxins - chemical synthesis ; Cytotoxins - chemistry ; Cytotoxins - toxicity ; Drug Evaluation, Preclinical ; HeLa Cells ; Humans ; Inhibitory Concentration 50 ; molecular modeling ; Molecular Structure ; Oxidation-Reduction ; Sulfhydryl Compounds - chemical synthesis ; Sulfhydryl Compounds - chemistry ; Sulfhydryl Compounds - toxicity ; Sulfur - chemistry ; tubulin interaction</subject><ispartof>Chemical biology & drug design, 2016-10, Vol.88 (4), p.519-533</ispartof><rights>2016 John Wiley & Sons A/S</rights><rights>2016 John Wiley & Sons A/S.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4706-6b0dc5f00f8aeb50e083f1cdb947e8e490cf144d460de3d140d236bab3c153543</citedby><cites>FETCH-LOGICAL-c4706-6b0dc5f00f8aeb50e083f1cdb947e8e490cf144d460de3d140d236bab3c153543</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fcbdd.12776$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fcbdd.12776$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27198732$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Konieczny, Marek T.</creatorcontrib><creatorcontrib>Buɬakowska, Anita</creatorcontrib><creatorcontrib>Pirska, Danuta</creatorcontrib><creatorcontrib>Konieczny, Wojciech</creatorcontrib><creatorcontrib>Skladanowski, Andrzej</creatorcontrib><creatorcontrib>Sabisz, Michal</creatorcontrib><creatorcontrib>Wojciechowski, Marek</creatorcontrib><creatorcontrib>Lemke, Krzysztof</creatorcontrib><title>Influence of S-Oxidation on Cytotoxic Activity of Oxathiole-Fused Chalcones</title><title>Chemical biology & drug design</title><addtitle>Chem Biol Drug Des</addtitle><description>Synthesis, in vitro cytotoxic activity, and interaction with tubulin of oxidized, isomeric 1‐(5‐alkoxybenzo[d][1,3]oxathiol‐6‐yl)‐3‐phenylprop‐2‐en‐1‐ones and 1‐(6‐alkoxybenzo[d][1,3]oxathiol‐5‐yl)‐3‐phenylprop‐2‐en‐1‐ones are described. Most of the compounds demonstrated cytotoxic activity at submicromolar concentrations. It was found that oxidation of sulfur atom of the oxathiole‐fused chalcones strongly influenced activity of the parent compounds, and that depending on relative position of the sulfur atom in the molecule, the activity was either increased or diminished. For isomers with sulfur atom para to the chalcone carbonyl group, oxidation led to increase in activity, while for isomers with sulfur atom meta to the carbonyl the activity dropped down. It was demonstrated that the compounds interact with tubulin at the colchicine binding site, and the interaction was evaluated using molecular modeling. It was concluded that the observed profound influence of oxidation of the sulfur atom on cytotoxic activity cannot be solely related to interaction of the compounds with tubulin.
Most of the compounds demonstrated cytotoxic activity at submicromolar concentrations. Oxidation of sulfur atom of the oxathiole‐fused chalcones strongly influenced activity of the parent compounds, and depending on relative position of the sulfur atom in the molecule, the activity was either increased or diminished. It was demonstrated that the compounds interact with tubulin at the colchicine binding site.</description><subject>benzoxathiole oxidation</subject><subject>Cell Line, Tumor</subject><subject>Cell Survival - drug effects</subject><subject>chalcone</subject><subject>Chalcones - chemical synthesis</subject><subject>Chalcones - chemistry</subject><subject>Chalcones - toxicity</subject><subject>cytotoxic activity</subject><subject>Cytotoxins - chemical synthesis</subject><subject>Cytotoxins - chemistry</subject><subject>Cytotoxins - toxicity</subject><subject>Drug Evaluation, Preclinical</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Inhibitory Concentration 50</subject><subject>molecular modeling</subject><subject>Molecular Structure</subject><subject>Oxidation-Reduction</subject><subject>Sulfhydryl Compounds - chemical synthesis</subject><subject>Sulfhydryl Compounds - chemistry</subject><subject>Sulfhydryl Compounds - toxicity</subject><subject>Sulfur - chemistry</subject><subject>tubulin interaction</subject><issn>1747-0277</issn><issn>1747-0285</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkMtOwzAQRS0E4r3hA1CWCCkwfiROlpBCQSC6AMTScuyJMKQxxAm0f09KoUvEaKSZxblncQk5oHBChzk1pbUnlEmZrpFtKoWMgWXJ-uqXcovshPACIETCsk2yxSTNM8nZNrm5bqq6x8Zg5KvoPp7MnNWd8000bDHvfOdnzkRnpnMfrpsvoMlMd8_O1xhf9gFtVDzr2vgGwx7ZqHQdcP_n7pLHy4uH4iq-nYyvi7Pb2AgJaZyWYE1SAVSZxjIBhIxX1NgyFxIzFDmYigphRQoWuaUCLONpqUtuaMITwXfJ0dL71vr3HkOnpi4YrGvdoO-DohmTOaUc2H9QSEEM3gE9XqKm9SG0WKm31k11O1cU1KJntehZffc8wIc_3r6col2hv8UOAF0Cn67G-R8qVZyPRr_SeJlxocPZKqPbV5VKLhP1dDdWYsyS_Apy9cC_AAgvlZI</recordid><startdate>201610</startdate><enddate>201610</enddate><creator>Konieczny, Marek T.</creator><creator>Buɬakowska, Anita</creator><creator>Pirska, Danuta</creator><creator>Konieczny, Wojciech</creator><creator>Skladanowski, Andrzej</creator><creator>Sabisz, Michal</creator><creator>Wojciechowski, Marek</creator><creator>Lemke, Krzysztof</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><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><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>201610</creationdate><title>Influence of S-Oxidation on Cytotoxic Activity of Oxathiole-Fused Chalcones</title><author>Konieczny, Marek T. ; Buɬakowska, Anita ; Pirska, Danuta ; Konieczny, Wojciech ; Skladanowski, Andrzej ; Sabisz, Michal ; Wojciechowski, Marek ; Lemke, Krzysztof</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4706-6b0dc5f00f8aeb50e083f1cdb947e8e490cf144d460de3d140d236bab3c153543</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>benzoxathiole oxidation</topic><topic>Cell Line, Tumor</topic><topic>Cell Survival - drug effects</topic><topic>chalcone</topic><topic>Chalcones - chemical synthesis</topic><topic>Chalcones - chemistry</topic><topic>Chalcones - toxicity</topic><topic>cytotoxic activity</topic><topic>Cytotoxins - chemical synthesis</topic><topic>Cytotoxins - chemistry</topic><topic>Cytotoxins - toxicity</topic><topic>Drug Evaluation, Preclinical</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Inhibitory Concentration 50</topic><topic>molecular modeling</topic><topic>Molecular Structure</topic><topic>Oxidation-Reduction</topic><topic>Sulfhydryl Compounds - chemical synthesis</topic><topic>Sulfhydryl Compounds - chemistry</topic><topic>Sulfhydryl Compounds - toxicity</topic><topic>Sulfur - chemistry</topic><topic>tubulin interaction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Konieczny, Marek T.</creatorcontrib><creatorcontrib>Buɬakowska, Anita</creatorcontrib><creatorcontrib>Pirska, Danuta</creatorcontrib><creatorcontrib>Konieczny, Wojciech</creatorcontrib><creatorcontrib>Skladanowski, Andrzej</creatorcontrib><creatorcontrib>Sabisz, Michal</creatorcontrib><creatorcontrib>Wojciechowski, Marek</creatorcontrib><creatorcontrib>Lemke, Krzysztof</creatorcontrib><collection>Istex</collection><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><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Chemical biology & drug design</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Konieczny, Marek T.</au><au>Buɬakowska, Anita</au><au>Pirska, Danuta</au><au>Konieczny, Wojciech</au><au>Skladanowski, Andrzej</au><au>Sabisz, Michal</au><au>Wojciechowski, Marek</au><au>Lemke, Krzysztof</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Influence of S-Oxidation on Cytotoxic Activity of Oxathiole-Fused Chalcones</atitle><jtitle>Chemical biology & drug design</jtitle><addtitle>Chem Biol Drug Des</addtitle><date>2016-10</date><risdate>2016</risdate><volume>88</volume><issue>4</issue><spage>519</spage><epage>533</epage><pages>519-533</pages><issn>1747-0277</issn><eissn>1747-0285</eissn><abstract>Synthesis, in vitro cytotoxic activity, and interaction with tubulin of oxidized, isomeric 1‐(5‐alkoxybenzo[d][1,3]oxathiol‐6‐yl)‐3‐phenylprop‐2‐en‐1‐ones and 1‐(6‐alkoxybenzo[d][1,3]oxathiol‐5‐yl)‐3‐phenylprop‐2‐en‐1‐ones are described. Most of the compounds demonstrated cytotoxic activity at submicromolar concentrations. It was found that oxidation of sulfur atom of the oxathiole‐fused chalcones strongly influenced activity of the parent compounds, and that depending on relative position of the sulfur atom in the molecule, the activity was either increased or diminished. For isomers with sulfur atom para to the chalcone carbonyl group, oxidation led to increase in activity, while for isomers with sulfur atom meta to the carbonyl the activity dropped down. It was demonstrated that the compounds interact with tubulin at the colchicine binding site, and the interaction was evaluated using molecular modeling. It was concluded that the observed profound influence of oxidation of the sulfur atom on cytotoxic activity cannot be solely related to interaction of the compounds with tubulin.
Most of the compounds demonstrated cytotoxic activity at submicromolar concentrations. Oxidation of sulfur atom of the oxathiole‐fused chalcones strongly influenced activity of the parent compounds, and depending on relative position of the sulfur atom in the molecule, the activity was either increased or diminished. It was demonstrated that the compounds interact with tubulin at the colchicine binding site.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>27198732</pmid><doi>10.1111/cbdd.12776</doi><tpages>15</tpages></addata></record> |
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| subjects | benzoxathiole oxidation Cell Line, Tumor Cell Survival - drug effects chalcone Chalcones - chemical synthesis Chalcones - chemistry Chalcones - toxicity cytotoxic activity Cytotoxins - chemical synthesis Cytotoxins - chemistry Cytotoxins - toxicity Drug Evaluation, Preclinical HeLa Cells Humans Inhibitory Concentration 50 molecular modeling Molecular Structure Oxidation-Reduction Sulfhydryl Compounds - chemical synthesis Sulfhydryl Compounds - chemistry Sulfhydryl Compounds - toxicity Sulfur - chemistry tubulin interaction |
| title | Influence of S-Oxidation on Cytotoxic Activity of Oxathiole-Fused Chalcones |
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