The Anticancer Activity and HSA Binding Properties of the Structurally Related Platinum (II) Complexes
The development of resistance and unwanted harmful interaction with other biomolecules instead of DNA are the major drawbacks for application of platinum (Pt) complexes in cancer chemotherapy. To conquer these problems, much works have been done so far to discover innovative Pt complexes. The object...
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| Veröffentlicht in: | Applied biochemistry and biotechnology 2012-06, Vol.167 (4), p.861-872 |
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| creator | Yousefi, Reza Aghevlian, Sadaf Mokhtari, Fatemeh Samouei, Hamidreza Rashidi, Mehdi Nabavizadeh, S. Masoud Tavaf, Zohreh Pouryasin, Zahra Niazi, Ali Faghihi, Reza Papari, Mohammad Mehdi |
| description | The development of resistance and unwanted harmful interaction with other biomolecules instead of DNA are the major drawbacks for application of platinum (Pt) complexes in cancer chemotherapy. To conquer these problems, much works have been done so far to discover innovative Pt complexes. The objective of the current study was to evaluate the anti cancer activities of a series of four and five-coordinated Pt(II) complexes, having deprotonated 2-phenyl pyridine (abbreviated as C^N), biphosphine moieties, i.e., dppm = bis(diphenylphosphino) methane (Ph
2
PCH
2
PPh
2
) and dppa = bis(diphenylphosphino)amine (Ph
2
PNHPPh
2
), as the non-leaving carrier groups. The growth inhibitory effect of the Pt complexes [Pt(C^N)(dppm)]PF
6
:
C
1
, [Pt(C^N)(dppa)]PF
6
:
C
2
, and [Pt(C^N)I(dppa)]:
C
3
, toward the cancer cell lines was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. In addition, the florescence quenching experiments of the interaction between human serum albumin (HSA) and the Pt complexes were performed in order to obtain the binding parameters and to evaluate the denaturing properties of these complexes upon binding to the general carrier protein of blood stream. The structure–activity relationship studies reveal that four-coordinated Pt complexes
C
1
and
C
2
with both significant hydrophobic and charge characteristics, not only exhibit strong antiproliferation activity toward the cancer cell lines, but also they display lower denaturing effect against carrier protein HSA. On the other hand, five-coordinated
C
3
complex with the unusual intermolecular NH…Pt hydrogen binding and the intrinsic ability for oligomerization, exhibits poor anticancer activity and strong denaturing property. The current study reveals that the balance between charge and hydrophobicity of the Pt complexes, also their hydrogen binding abilities and coordination mode are important for their anticancer activities. Moreover, this study may suggest
C
1
and
C
2
as the potential template structures for synthesis of new generation of four-coordinated Pt complexes with strong anticancer activities and weak denaturing effects against proteins. |
| doi_str_mv | 10.1007/s12010-012-9733-5 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1028027871</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1019095768</sourcerecordid><originalsourceid>FETCH-LOGICAL-c435t-5928b293d131fa143cc5ebd098c30b87231fc990dee2ddd58f38e4dd0a127bed3</originalsourceid><addsrcrecordid>eNqNkV1rFDEUhoModlv9Ad5IQIR6MZqTTHaSy-1S7ULBYuv1kEnO1JSZzJpkxP33Ztn1A0EQAgeS5z0nyUPIC2BvgbHmXQLOgFUMeKUbISr5iCxASl0xruExWTDeiIpzpU_IaUoPrIBKNk_JCefLsmqxIP3dF6SrkL01wWKkK5v9N5931ARHr25X9MIH58M9vYnTFmP2mOjU01xStznONs_RDMOOfsLBZHT0phQf5pGebzZv6HoatwN-x_SMPOnNkPD5sZ6Rz-8v79ZX1fXHD5v16rqytZC5kpqrjmvhQEBvoBbWSuwc08oK1qmGl22rNXOI3DknVS8U1s4xA7zp0Ikzcn7ou43T1xlTbkefLA6DCTjNqQXGVfkV1cB_oKCZls1SFfTVX-jDNMdQHrKn1BIARF0oOFA2TilF7Ntt9KOJuwK1e1_twVdbNLR7X60smZfHznM3ovuV-CmoAK-PgEnWDH0smnz6zS1LQ13vh_MDl8pRuMf45xX_Nf0HoOCrPQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1018611134</pqid></control><display><type>article</type><title>The Anticancer Activity and HSA Binding Properties of the Structurally Related Platinum (II) Complexes</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Yousefi, Reza ; Aghevlian, Sadaf ; Mokhtari, Fatemeh ; Samouei, Hamidreza ; Rashidi, Mehdi ; Nabavizadeh, S. Masoud ; Tavaf, Zohreh ; Pouryasin, Zahra ; Niazi, Ali ; Faghihi, Reza ; Papari, Mohammad Mehdi</creator><creatorcontrib>Yousefi, Reza ; Aghevlian, Sadaf ; Mokhtari, Fatemeh ; Samouei, Hamidreza ; Rashidi, Mehdi ; Nabavizadeh, S. Masoud ; Tavaf, Zohreh ; Pouryasin, Zahra ; Niazi, Ali ; Faghihi, Reza ; Papari, Mohammad Mehdi</creatorcontrib><description>The development of resistance and unwanted harmful interaction with other biomolecules instead of DNA are the major drawbacks for application of platinum (Pt) complexes in cancer chemotherapy. To conquer these problems, much works have been done so far to discover innovative Pt complexes. The objective of the current study was to evaluate the anti cancer activities of a series of four and five-coordinated Pt(II) complexes, having deprotonated 2-phenyl pyridine (abbreviated as C^N), biphosphine moieties, i.e., dppm = bis(diphenylphosphino) methane (Ph
2
PCH
2
PPh
2
) and dppa = bis(diphenylphosphino)amine (Ph
2
PNHPPh
2
), as the non-leaving carrier groups. The growth inhibitory effect of the Pt complexes [Pt(C^N)(dppm)]PF
6
:
C
1
, [Pt(C^N)(dppa)]PF
6
:
C
2
, and [Pt(C^N)I(dppa)]:
C
3
, toward the cancer cell lines was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. In addition, the florescence quenching experiments of the interaction between human serum albumin (HSA) and the Pt complexes were performed in order to obtain the binding parameters and to evaluate the denaturing properties of these complexes upon binding to the general carrier protein of blood stream. The structure–activity relationship studies reveal that four-coordinated Pt complexes
C
1
and
C
2
with both significant hydrophobic and charge characteristics, not only exhibit strong antiproliferation activity toward the cancer cell lines, but also they display lower denaturing effect against carrier protein HSA. On the other hand, five-coordinated
C
3
complex with the unusual intermolecular NH…Pt hydrogen binding and the intrinsic ability for oligomerization, exhibits poor anticancer activity and strong denaturing property. The current study reveals that the balance between charge and hydrophobicity of the Pt complexes, also their hydrogen binding abilities and coordination mode are important for their anticancer activities. Moreover, this study may suggest
C
1
and
C
2
as the potential template structures for synthesis of new generation of four-coordinated Pt complexes with strong anticancer activities and weak denaturing effects against proteins.</description><identifier>ISSN: 0273-2289</identifier><identifier>EISSN: 1559-0291</identifier><identifier>DOI: 10.1007/s12010-012-9733-5</identifier><identifier>PMID: 22622643</identifier><identifier>CODEN: ABIBDL</identifier><language>eng</language><publisher>New York: Springer-Verlag</publisher><subject>Antineoplastic Agents - chemistry ; Antineoplastic Agents - metabolism ; Antineoplastic Agents - pharmacology ; Binding sites ; Biochemistry ; Biological and medical sciences ; Biotechnology ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Chemistry ; Chemistry and Materials Science ; Chemotherapy ; Fundamental and applied biological sciences. Psychology ; Humans ; Molecular biology ; Organoplatinum Compounds - chemistry ; Organoplatinum Compounds - metabolism ; Organoplatinum Compounds - pharmacology ; Platinum ; Protein Binding ; Protein Denaturation - drug effects ; Proteins ; Serum Albumin - chemistry ; Serum Albumin - metabolism ; Spectrometry, Fluorescence</subject><ispartof>Applied biochemistry and biotechnology, 2012-06, Vol.167 (4), p.861-872</ispartof><rights>Springer Science+Business Media, LLC 2012</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c435t-5928b293d131fa143cc5ebd098c30b87231fc990dee2ddd58f38e4dd0a127bed3</citedby><cites>FETCH-LOGICAL-c435t-5928b293d131fa143cc5ebd098c30b87231fc990dee2ddd58f38e4dd0a127bed3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12010-012-9733-5$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12010-012-9733-5$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>315,782,786,27931,27932,41495,42564,51326</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26010944$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22622643$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yousefi, Reza</creatorcontrib><creatorcontrib>Aghevlian, Sadaf</creatorcontrib><creatorcontrib>Mokhtari, Fatemeh</creatorcontrib><creatorcontrib>Samouei, Hamidreza</creatorcontrib><creatorcontrib>Rashidi, Mehdi</creatorcontrib><creatorcontrib>Nabavizadeh, S. Masoud</creatorcontrib><creatorcontrib>Tavaf, Zohreh</creatorcontrib><creatorcontrib>Pouryasin, Zahra</creatorcontrib><creatorcontrib>Niazi, Ali</creatorcontrib><creatorcontrib>Faghihi, Reza</creatorcontrib><creatorcontrib>Papari, Mohammad Mehdi</creatorcontrib><title>The Anticancer Activity and HSA Binding Properties of the Structurally Related Platinum (II) Complexes</title><title>Applied biochemistry and biotechnology</title><addtitle>Appl Biochem Biotechnol</addtitle><addtitle>Appl Biochem Biotechnol</addtitle><description>The development of resistance and unwanted harmful interaction with other biomolecules instead of DNA are the major drawbacks for application of platinum (Pt) complexes in cancer chemotherapy. To conquer these problems, much works have been done so far to discover innovative Pt complexes. The objective of the current study was to evaluate the anti cancer activities of a series of four and five-coordinated Pt(II) complexes, having deprotonated 2-phenyl pyridine (abbreviated as C^N), biphosphine moieties, i.e., dppm = bis(diphenylphosphino) methane (Ph
2
PCH
2
PPh
2
) and dppa = bis(diphenylphosphino)amine (Ph
2
PNHPPh
2
), as the non-leaving carrier groups. The growth inhibitory effect of the Pt complexes [Pt(C^N)(dppm)]PF
6
:
C
1
, [Pt(C^N)(dppa)]PF
6
:
C
2
, and [Pt(C^N)I(dppa)]:
C
3
, toward the cancer cell lines was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. In addition, the florescence quenching experiments of the interaction between human serum albumin (HSA) and the Pt complexes were performed in order to obtain the binding parameters and to evaluate the denaturing properties of these complexes upon binding to the general carrier protein of blood stream. The structure–activity relationship studies reveal that four-coordinated Pt complexes
C
1
and
C
2
with both significant hydrophobic and charge characteristics, not only exhibit strong antiproliferation activity toward the cancer cell lines, but also they display lower denaturing effect against carrier protein HSA. On the other hand, five-coordinated
C
3
complex with the unusual intermolecular NH…Pt hydrogen binding and the intrinsic ability for oligomerization, exhibits poor anticancer activity and strong denaturing property. The current study reveals that the balance between charge and hydrophobicity of the Pt complexes, also their hydrogen binding abilities and coordination mode are important for their anticancer activities. Moreover, this study may suggest
C
1
and
C
2
as the potential template structures for synthesis of new generation of four-coordinated Pt complexes with strong anticancer activities and weak denaturing effects against proteins.</description><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - metabolism</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Binding sites</subject><subject>Biochemistry</subject><subject>Biological and medical sciences</subject><subject>Biotechnology</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Chemistry</subject><subject>Chemistry and Materials Science</subject><subject>Chemotherapy</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Molecular biology</subject><subject>Organoplatinum Compounds - chemistry</subject><subject>Organoplatinum Compounds - metabolism</subject><subject>Organoplatinum Compounds - pharmacology</subject><subject>Platinum</subject><subject>Protein Binding</subject><subject>Protein Denaturation - drug effects</subject><subject>Proteins</subject><subject>Serum Albumin - chemistry</subject><subject>Serum Albumin - metabolism</subject><subject>Spectrometry, Fluorescence</subject><issn>0273-2289</issn><issn>1559-0291</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqNkV1rFDEUhoModlv9Ad5IQIR6MZqTTHaSy-1S7ULBYuv1kEnO1JSZzJpkxP33Ztn1A0EQAgeS5z0nyUPIC2BvgbHmXQLOgFUMeKUbISr5iCxASl0xruExWTDeiIpzpU_IaUoPrIBKNk_JCefLsmqxIP3dF6SrkL01wWKkK5v9N5931ARHr25X9MIH58M9vYnTFmP2mOjU01xStznONs_RDMOOfsLBZHT0phQf5pGebzZv6HoatwN-x_SMPOnNkPD5sZ6Rz-8v79ZX1fXHD5v16rqytZC5kpqrjmvhQEBvoBbWSuwc08oK1qmGl22rNXOI3DknVS8U1s4xA7zp0Ikzcn7ou43T1xlTbkefLA6DCTjNqQXGVfkV1cB_oKCZls1SFfTVX-jDNMdQHrKn1BIARF0oOFA2TilF7Ntt9KOJuwK1e1_twVdbNLR7X60smZfHznM3ovuV-CmoAK-PgEnWDH0smnz6zS1LQ13vh_MDl8pRuMf45xX_Nf0HoOCrPQ</recordid><startdate>20120601</startdate><enddate>20120601</enddate><creator>Yousefi, Reza</creator><creator>Aghevlian, Sadaf</creator><creator>Mokhtari, Fatemeh</creator><creator>Samouei, Hamidreza</creator><creator>Rashidi, Mehdi</creator><creator>Nabavizadeh, S. Masoud</creator><creator>Tavaf, Zohreh</creator><creator>Pouryasin, Zahra</creator><creator>Niazi, Ali</creator><creator>Faghihi, Reza</creator><creator>Papari, Mohammad Mehdi</creator><general>Springer-Verlag</general><general>Springer</general><general>Springer Nature B.V</general><scope>IQODW</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>3V.</scope><scope>7ST</scope><scope>7T7</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>SOI</scope><scope>7X8</scope><scope>7QO</scope></search><sort><creationdate>20120601</creationdate><title>The Anticancer Activity and HSA Binding Properties of the Structurally Related Platinum (II) Complexes</title><author>Yousefi, Reza ; Aghevlian, Sadaf ; Mokhtari, Fatemeh ; Samouei, Hamidreza ; Rashidi, Mehdi ; Nabavizadeh, S. Masoud ; Tavaf, Zohreh ; Pouryasin, Zahra ; Niazi, Ali ; Faghihi, Reza ; Papari, Mohammad Mehdi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c435t-5928b293d131fa143cc5ebd098c30b87231fc990dee2ddd58f38e4dd0a127bed3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - metabolism</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Binding sites</topic><topic>Biochemistry</topic><topic>Biological and medical sciences</topic><topic>Biotechnology</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Chemistry</topic><topic>Chemistry and Materials Science</topic><topic>Chemotherapy</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Molecular biology</topic><topic>Organoplatinum Compounds - chemistry</topic><topic>Organoplatinum Compounds - metabolism</topic><topic>Organoplatinum Compounds - pharmacology</topic><topic>Platinum</topic><topic>Protein Binding</topic><topic>Protein Denaturation - drug effects</topic><topic>Proteins</topic><topic>Serum Albumin - chemistry</topic><topic>Serum Albumin - metabolism</topic><topic>Spectrometry, Fluorescence</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yousefi, Reza</creatorcontrib><creatorcontrib>Aghevlian, Sadaf</creatorcontrib><creatorcontrib>Mokhtari, Fatemeh</creatorcontrib><creatorcontrib>Samouei, Hamidreza</creatorcontrib><creatorcontrib>Rashidi, Mehdi</creatorcontrib><creatorcontrib>Nabavizadeh, S. Masoud</creatorcontrib><creatorcontrib>Tavaf, Zohreh</creatorcontrib><creatorcontrib>Pouryasin, Zahra</creatorcontrib><creatorcontrib>Niazi, Ali</creatorcontrib><creatorcontrib>Faghihi, Reza</creatorcontrib><creatorcontrib>Papari, Mohammad Mehdi</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Environment Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Nucleic Acids Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>Environment Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><jtitle>Applied biochemistry and biotechnology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yousefi, Reza</au><au>Aghevlian, Sadaf</au><au>Mokhtari, Fatemeh</au><au>Samouei, Hamidreza</au><au>Rashidi, Mehdi</au><au>Nabavizadeh, S. Masoud</au><au>Tavaf, Zohreh</au><au>Pouryasin, Zahra</au><au>Niazi, Ali</au><au>Faghihi, Reza</au><au>Papari, Mohammad Mehdi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Anticancer Activity and HSA Binding Properties of the Structurally Related Platinum (II) Complexes</atitle><jtitle>Applied biochemistry and biotechnology</jtitle><stitle>Appl Biochem Biotechnol</stitle><addtitle>Appl Biochem Biotechnol</addtitle><date>2012-06-01</date><risdate>2012</risdate><volume>167</volume><issue>4</issue><spage>861</spage><epage>872</epage><pages>861-872</pages><issn>0273-2289</issn><eissn>1559-0291</eissn><coden>ABIBDL</coden><abstract>The development of resistance and unwanted harmful interaction with other biomolecules instead of DNA are the major drawbacks for application of platinum (Pt) complexes in cancer chemotherapy. To conquer these problems, much works have been done so far to discover innovative Pt complexes. The objective of the current study was to evaluate the anti cancer activities of a series of four and five-coordinated Pt(II) complexes, having deprotonated 2-phenyl pyridine (abbreviated as C^N), biphosphine moieties, i.e., dppm = bis(diphenylphosphino) methane (Ph
2
PCH
2
PPh
2
) and dppa = bis(diphenylphosphino)amine (Ph
2
PNHPPh
2
), as the non-leaving carrier groups. The growth inhibitory effect of the Pt complexes [Pt(C^N)(dppm)]PF
6
:
C
1
, [Pt(C^N)(dppa)]PF
6
:
C
2
, and [Pt(C^N)I(dppa)]:
C
3
, toward the cancer cell lines was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. In addition, the florescence quenching experiments of the interaction between human serum albumin (HSA) and the Pt complexes were performed in order to obtain the binding parameters and to evaluate the denaturing properties of these complexes upon binding to the general carrier protein of blood stream. The structure–activity relationship studies reveal that four-coordinated Pt complexes
C
1
and
C
2
with both significant hydrophobic and charge characteristics, not only exhibit strong antiproliferation activity toward the cancer cell lines, but also they display lower denaturing effect against carrier protein HSA. On the other hand, five-coordinated
C
3
complex with the unusual intermolecular NH…Pt hydrogen binding and the intrinsic ability for oligomerization, exhibits poor anticancer activity and strong denaturing property. The current study reveals that the balance between charge and hydrophobicity of the Pt complexes, also their hydrogen binding abilities and coordination mode are important for their anticancer activities. Moreover, this study may suggest
C
1
and
C
2
as the potential template structures for synthesis of new generation of four-coordinated Pt complexes with strong anticancer activities and weak denaturing effects against proteins.</abstract><cop>New York</cop><pub>Springer-Verlag</pub><pmid>22622643</pmid><doi>10.1007/s12010-012-9733-5</doi><tpages>12</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Applied biochemistry and biotechnology, 2012-06, Vol.167 (4), p.861-872 |
| issn | 0273-2289 1559-0291 |
| language | eng |
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| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Antineoplastic Agents - chemistry Antineoplastic Agents - metabolism Antineoplastic Agents - pharmacology Binding sites Biochemistry Biological and medical sciences Biotechnology Cell Line, Tumor Cell Proliferation - drug effects Chemistry Chemistry and Materials Science Chemotherapy Fundamental and applied biological sciences. Psychology Humans Molecular biology Organoplatinum Compounds - chemistry Organoplatinum Compounds - metabolism Organoplatinum Compounds - pharmacology Platinum Protein Binding Protein Denaturation - drug effects Proteins Serum Albumin - chemistry Serum Albumin - metabolism Spectrometry, Fluorescence |
| title | The Anticancer Activity and HSA Binding Properties of the Structurally Related Platinum (II) Complexes |
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