Manganese(I) tricarbonyl complexes as potential anticancer agents
The antiproliferative activity of [Mn(CO) 3 (N^N)Br] (N^N = phendione 1 , bipy 3 ) and of the two newly synthesized Mn complexes [Mn(CO) 3 (acridine)(phendione)]OTf ( 2 ) and [Mn(CO) 3 (di-triazole)Br] ( 4 ) has been evaluated by MTS against three tumor cell lines A2780 (ovarian carcinoma), HCT116 (...
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| Veröffentlicht in: | Journal of biological inorganic chemistry 2022-02, Vol.27 (1), p.49-64 |
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| creator | Lenis-Rojas, Oscar A. Carvalho, Beatriz Cabral, Rui Silva, Margarida Friães, Sofia Roma-Rodrigues, Catarina Meireles, Marta S. H. Gomes, Clara S. B. Fernández, Jhonathan A. A. Vila, Sabela F. Rubiolo, Juan A. Sanchez, Laura Baptista, Pedro V. Fernandes, Alexandra R. Royo, Beatriz |
| description | The antiproliferative activity of [Mn(CO)
3
(N^N)Br] (N^N = phendione
1
, bipy
3
) and of the two newly synthesized Mn complexes [Mn(CO)
3
(acridine)(phendione)]OTf (
2
) and [Mn(CO)
3
(di-triazole)Br] (
4
) has been evaluated by MTS against three tumor cell lines A2780 (ovarian carcinoma), HCT116 (colorectal carcinoma), HCT116doxR (colorectal carcinoma resistant to doxorubicin), and in human dermal fibroblasts. The antiproliferative assay showed a dose-dependent effect higher in complex
1
and
2
with a selectivity toward ovarian carcinoma cell line 21 times higher than in human fibroblasts. Exposure of A2780 cells to IC
50
concentrations of complex
1
and
2
led to an increase of reactive oxygen species that led to the activation of cell death mechanisms, namely via intrinsic apoptosis for
2
and autophagy and extrinsic apoptosis for
1
. Both complexes do not target DNA or interfere with cell cycle progression but are able to potentiate cell migration and neovascularization (for
2
) an indicative that their application might be directed for initial tumor stages to avoid tumor invasion and metastization and opening a new avenue for complex
2
application in regenerative medicine. Interestingly, both complexes do not show toxicity in both in vivo models (CAM and zebrafish).
Graphical abstract |
| doi_str_mv | 10.1007/s00775-021-01910-7 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2590084774</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2628157430</sourcerecordid><originalsourceid>FETCH-LOGICAL-c375t-60a2e66bf624c2102c1958303e2c5fa9bb75530f40c31d66298ffa2470514fc83</originalsourceid><addsrcrecordid>eNp9kE1LAzEQhoMotlb_gAdZ8FIP0cnXZvcoxY9CxYueQzZNypb9MtkF---NblXw4GUGkmfeGR6EzglcEwB5E2KRAgMlGEhOAMsDNCWcUUwYlYdoCjnPcUaFnKCTELYAwAQRx2jCuCQslim6fdLNRjc22PnyKul9abQv2mZXJaatu8q-25DokHRtb5u-1FWiYzO6MdYnehPfwik6croK9mzfZ-j1_u5l8YhXzw_Lxe0KGyZFj1PQ1KZp4VLKDSVADclFxoBZaoTTeVFIIRg4DoaRdZrSPHNOUy5BEO5MxmZoPuZ2vn0bbOhVXQZjqype3w5BUZEDZFxKHtHLP-i2HXwTr1M0pRkRkYFI0ZEyvg3BW6c6X9ba7xQB9SlYjYJVFKy-BCsZhy720UNR2_XPyLfRCLARCPGr2Vj_u_uf2A_T64Pg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2628157430</pqid></control><display><type>article</type><title>Manganese(I) tricarbonyl complexes as potential anticancer agents</title><source>MEDLINE</source><source>SpringerLink</source><creator>Lenis-Rojas, Oscar A. ; Carvalho, Beatriz ; Cabral, Rui ; Silva, Margarida ; Friães, Sofia ; Roma-Rodrigues, Catarina ; Meireles, Marta S. H. ; Gomes, Clara S. B. ; Fernández, Jhonathan A. A. ; Vila, Sabela F. ; Rubiolo, Juan A. ; Sanchez, Laura ; Baptista, Pedro V. ; Fernandes, Alexandra R. ; Royo, Beatriz</creator><creatorcontrib>Lenis-Rojas, Oscar A. ; Carvalho, Beatriz ; Cabral, Rui ; Silva, Margarida ; Friães, Sofia ; Roma-Rodrigues, Catarina ; Meireles, Marta S. H. ; Gomes, Clara S. B. ; Fernández, Jhonathan A. A. ; Vila, Sabela F. ; Rubiolo, Juan A. ; Sanchez, Laura ; Baptista, Pedro V. ; Fernandes, Alexandra R. ; Royo, Beatriz</creatorcontrib><description>The antiproliferative activity of [Mn(CO)
3
(N^N)Br] (N^N = phendione
1
, bipy
3
) and of the two newly synthesized Mn complexes [Mn(CO)
3
(acridine)(phendione)]OTf (
2
) and [Mn(CO)
3
(di-triazole)Br] (
4
) has been evaluated by MTS against three tumor cell lines A2780 (ovarian carcinoma), HCT116 (colorectal carcinoma), HCT116doxR (colorectal carcinoma resistant to doxorubicin), and in human dermal fibroblasts. The antiproliferative assay showed a dose-dependent effect higher in complex
1
and
2
with a selectivity toward ovarian carcinoma cell line 21 times higher than in human fibroblasts. Exposure of A2780 cells to IC
50
concentrations of complex
1
and
2
led to an increase of reactive oxygen species that led to the activation of cell death mechanisms, namely via intrinsic apoptosis for
2
and autophagy and extrinsic apoptosis for
1
. Both complexes do not target DNA or interfere with cell cycle progression but are able to potentiate cell migration and neovascularization (for
2
) an indicative that their application might be directed for initial tumor stages to avoid tumor invasion and metastization and opening a new avenue for complex
2
application in regenerative medicine. Interestingly, both complexes do not show toxicity in both in vivo models (CAM and zebrafish).
Graphical abstract</description><identifier>ISSN: 0949-8257</identifier><identifier>EISSN: 1432-1327</identifier><identifier>DOI: 10.1007/s00775-021-01910-7</identifier><identifier>PMID: 34713347</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Acridine ; Animals ; Antineoplastic Agents - chemistry ; Antitumor agents ; Apoptosis ; Autophagy ; Biochemistry ; Biomedical and Life Sciences ; Cancer ; Cell activation ; Cell cycle ; Cell death ; Cell Line, Tumor ; Cell migration ; Cell Proliferation ; Colorectal carcinoma ; Coordination Complexes - chemistry ; Doxorubicin ; Female ; Fibroblasts ; Humans ; Inorganic chemistry ; Life Sciences ; Manganese ; Microbiology ; Original Paper ; Ovarian carcinoma ; Ovarian Neoplasms - pathology ; Ovaries ; Reactive oxygen species ; Regenerative medicine ; Toxicity ; Tumor cell lines ; Tumors ; Vascularization ; Zebrafish</subject><ispartof>Journal of biological inorganic chemistry, 2022-02, Vol.27 (1), p.49-64</ispartof><rights>The Author(s), under exclusive licence to Society for Biological Inorganic Chemistry (SBIC) 2021</rights><rights>2021. The Author(s), under exclusive licence to Society for Biological Inorganic Chemistry (SBIC).</rights><rights>The Author(s), under exclusive licence to Society for Biological Inorganic Chemistry (SBIC) 2021.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-60a2e66bf624c2102c1958303e2c5fa9bb75530f40c31d66298ffa2470514fc83</citedby><cites>FETCH-LOGICAL-c375t-60a2e66bf624c2102c1958303e2c5fa9bb75530f40c31d66298ffa2470514fc83</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/s00775-021-01910-7$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00775-021-01910-7$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34713347$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lenis-Rojas, Oscar A.</creatorcontrib><creatorcontrib>Carvalho, Beatriz</creatorcontrib><creatorcontrib>Cabral, Rui</creatorcontrib><creatorcontrib>Silva, Margarida</creatorcontrib><creatorcontrib>Friães, Sofia</creatorcontrib><creatorcontrib>Roma-Rodrigues, Catarina</creatorcontrib><creatorcontrib>Meireles, Marta S. H.</creatorcontrib><creatorcontrib>Gomes, Clara S. B.</creatorcontrib><creatorcontrib>Fernández, Jhonathan A. A.</creatorcontrib><creatorcontrib>Vila, Sabela F.</creatorcontrib><creatorcontrib>Rubiolo, Juan A.</creatorcontrib><creatorcontrib>Sanchez, Laura</creatorcontrib><creatorcontrib>Baptista, Pedro V.</creatorcontrib><creatorcontrib>Fernandes, Alexandra R.</creatorcontrib><creatorcontrib>Royo, Beatriz</creatorcontrib><title>Manganese(I) tricarbonyl complexes as potential anticancer agents</title><title>Journal of biological inorganic chemistry</title><addtitle>J Biol Inorg Chem</addtitle><addtitle>J Biol Inorg Chem</addtitle><description>The antiproliferative activity of [Mn(CO)
3
(N^N)Br] (N^N = phendione
1
, bipy
3
) and of the two newly synthesized Mn complexes [Mn(CO)
3
(acridine)(phendione)]OTf (
2
) and [Mn(CO)
3
(di-triazole)Br] (
4
) has been evaluated by MTS against three tumor cell lines A2780 (ovarian carcinoma), HCT116 (colorectal carcinoma), HCT116doxR (colorectal carcinoma resistant to doxorubicin), and in human dermal fibroblasts. The antiproliferative assay showed a dose-dependent effect higher in complex
1
and
2
with a selectivity toward ovarian carcinoma cell line 21 times higher than in human fibroblasts. Exposure of A2780 cells to IC
50
concentrations of complex
1
and
2
led to an increase of reactive oxygen species that led to the activation of cell death mechanisms, namely via intrinsic apoptosis for
2
and autophagy and extrinsic apoptosis for
1
. Both complexes do not target DNA or interfere with cell cycle progression but are able to potentiate cell migration and neovascularization (for
2
) an indicative that their application might be directed for initial tumor stages to avoid tumor invasion and metastization and opening a new avenue for complex
2
application in regenerative medicine. Interestingly, both complexes do not show toxicity in both in vivo models (CAM and zebrafish).
Graphical abstract</description><subject>Acridine</subject><subject>Animals</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antitumor agents</subject><subject>Apoptosis</subject><subject>Autophagy</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Cancer</subject><subject>Cell activation</subject><subject>Cell cycle</subject><subject>Cell death</subject><subject>Cell Line, Tumor</subject><subject>Cell migration</subject><subject>Cell Proliferation</subject><subject>Colorectal carcinoma</subject><subject>Coordination Complexes - chemistry</subject><subject>Doxorubicin</subject><subject>Female</subject><subject>Fibroblasts</subject><subject>Humans</subject><subject>Inorganic chemistry</subject><subject>Life Sciences</subject><subject>Manganese</subject><subject>Microbiology</subject><subject>Original Paper</subject><subject>Ovarian carcinoma</subject><subject>Ovarian Neoplasms - pathology</subject><subject>Ovaries</subject><subject>Reactive oxygen species</subject><subject>Regenerative medicine</subject><subject>Toxicity</subject><subject>Tumor cell lines</subject><subject>Tumors</subject><subject>Vascularization</subject><subject>Zebrafish</subject><issn>0949-8257</issn><issn>1432-1327</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1LAzEQhoMotlb_gAdZ8FIP0cnXZvcoxY9CxYueQzZNypb9MtkF---NblXw4GUGkmfeGR6EzglcEwB5E2KRAgMlGEhOAMsDNCWcUUwYlYdoCjnPcUaFnKCTELYAwAQRx2jCuCQslim6fdLNRjc22PnyKul9abQv2mZXJaatu8q-25DokHRtb5u-1FWiYzO6MdYnehPfwik6croK9mzfZ-j1_u5l8YhXzw_Lxe0KGyZFj1PQ1KZp4VLKDSVADclFxoBZaoTTeVFIIRg4DoaRdZrSPHNOUy5BEO5MxmZoPuZ2vn0bbOhVXQZjqype3w5BUZEDZFxKHtHLP-i2HXwTr1M0pRkRkYFI0ZEyvg3BW6c6X9ba7xQB9SlYjYJVFKy-BCsZhy720UNR2_XPyLfRCLARCPGr2Vj_u_uf2A_T64Pg</recordid><startdate>20220201</startdate><enddate>20220201</enddate><creator>Lenis-Rojas, Oscar A.</creator><creator>Carvalho, Beatriz</creator><creator>Cabral, Rui</creator><creator>Silva, Margarida</creator><creator>Friães, Sofia</creator><creator>Roma-Rodrigues, Catarina</creator><creator>Meireles, Marta S. H.</creator><creator>Gomes, Clara S. B.</creator><creator>Fernández, Jhonathan A. A.</creator><creator>Vila, Sabela F.</creator><creator>Rubiolo, Juan A.</creator><creator>Sanchez, Laura</creator><creator>Baptista, Pedro V.</creator><creator>Fernandes, Alexandra R.</creator><creator>Royo, Beatriz</creator><general>Springer International Publishing</general><general>Springer Nature B.V</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>20220201</creationdate><title>Manganese(I) tricarbonyl complexes as potential anticancer agents</title><author>Lenis-Rojas, Oscar A. ; Carvalho, Beatriz ; Cabral, Rui ; Silva, Margarida ; Friães, Sofia ; Roma-Rodrigues, Catarina ; Meireles, Marta S. H. ; Gomes, Clara S. B. ; Fernández, Jhonathan A. A. ; Vila, Sabela F. ; Rubiolo, Juan A. ; Sanchez, Laura ; Baptista, Pedro V. ; Fernandes, Alexandra R. ; Royo, Beatriz</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-60a2e66bf624c2102c1958303e2c5fa9bb75530f40c31d66298ffa2470514fc83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Acridine</topic><topic>Animals</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Antitumor agents</topic><topic>Apoptosis</topic><topic>Autophagy</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Cancer</topic><topic>Cell activation</topic><topic>Cell cycle</topic><topic>Cell death</topic><topic>Cell Line, Tumor</topic><topic>Cell migration</topic><topic>Cell Proliferation</topic><topic>Colorectal carcinoma</topic><topic>Coordination Complexes - chemistry</topic><topic>Doxorubicin</topic><topic>Female</topic><topic>Fibroblasts</topic><topic>Humans</topic><topic>Inorganic chemistry</topic><topic>Life Sciences</topic><topic>Manganese</topic><topic>Microbiology</topic><topic>Original Paper</topic><topic>Ovarian carcinoma</topic><topic>Ovarian Neoplasms - pathology</topic><topic>Ovaries</topic><topic>Reactive oxygen species</topic><topic>Regenerative medicine</topic><topic>Toxicity</topic><topic>Tumor cell lines</topic><topic>Tumors</topic><topic>Vascularization</topic><topic>Zebrafish</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lenis-Rojas, Oscar A.</creatorcontrib><creatorcontrib>Carvalho, Beatriz</creatorcontrib><creatorcontrib>Cabral, Rui</creatorcontrib><creatorcontrib>Silva, Margarida</creatorcontrib><creatorcontrib>Friães, Sofia</creatorcontrib><creatorcontrib>Roma-Rodrigues, Catarina</creatorcontrib><creatorcontrib>Meireles, Marta S. H.</creatorcontrib><creatorcontrib>Gomes, Clara S. B.</creatorcontrib><creatorcontrib>Fernández, Jhonathan A. A.</creatorcontrib><creatorcontrib>Vila, Sabela F.</creatorcontrib><creatorcontrib>Rubiolo, Juan A.</creatorcontrib><creatorcontrib>Sanchez, Laura</creatorcontrib><creatorcontrib>Baptista, Pedro V.</creatorcontrib><creatorcontrib>Fernandes, Alexandra R.</creatorcontrib><creatorcontrib>Royo, Beatriz</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>Journal of biological inorganic chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lenis-Rojas, Oscar A.</au><au>Carvalho, Beatriz</au><au>Cabral, Rui</au><au>Silva, Margarida</au><au>Friães, Sofia</au><au>Roma-Rodrigues, Catarina</au><au>Meireles, Marta S. H.</au><au>Gomes, Clara S. B.</au><au>Fernández, Jhonathan A. A.</au><au>Vila, Sabela F.</au><au>Rubiolo, Juan A.</au><au>Sanchez, Laura</au><au>Baptista, Pedro V.</au><au>Fernandes, Alexandra R.</au><au>Royo, Beatriz</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Manganese(I) tricarbonyl complexes as potential anticancer agents</atitle><jtitle>Journal of biological inorganic chemistry</jtitle><stitle>J Biol Inorg Chem</stitle><addtitle>J Biol Inorg Chem</addtitle><date>2022-02-01</date><risdate>2022</risdate><volume>27</volume><issue>1</issue><spage>49</spage><epage>64</epage><pages>49-64</pages><issn>0949-8257</issn><eissn>1432-1327</eissn><abstract>The antiproliferative activity of [Mn(CO)
3
(N^N)Br] (N^N = phendione
1
, bipy
3
) and of the two newly synthesized Mn complexes [Mn(CO)
3
(acridine)(phendione)]OTf (
2
) and [Mn(CO)
3
(di-triazole)Br] (
4
) has been evaluated by MTS against three tumor cell lines A2780 (ovarian carcinoma), HCT116 (colorectal carcinoma), HCT116doxR (colorectal carcinoma resistant to doxorubicin), and in human dermal fibroblasts. The antiproliferative assay showed a dose-dependent effect higher in complex
1
and
2
with a selectivity toward ovarian carcinoma cell line 21 times higher than in human fibroblasts. Exposure of A2780 cells to IC
50
concentrations of complex
1
and
2
led to an increase of reactive oxygen species that led to the activation of cell death mechanisms, namely via intrinsic apoptosis for
2
and autophagy and extrinsic apoptosis for
1
. Both complexes do not target DNA or interfere with cell cycle progression but are able to potentiate cell migration and neovascularization (for
2
) an indicative that their application might be directed for initial tumor stages to avoid tumor invasion and metastization and opening a new avenue for complex
2
application in regenerative medicine. Interestingly, both complexes do not show toxicity in both in vivo models (CAM and zebrafish).
Graphical abstract</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>34713347</pmid><doi>10.1007/s00775-021-01910-7</doi><tpages>16</tpages></addata></record> |
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| language | eng |
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| source | MEDLINE; SpringerLink |
| subjects | Acridine Animals Antineoplastic Agents - chemistry Antitumor agents Apoptosis Autophagy Biochemistry Biomedical and Life Sciences Cancer Cell activation Cell cycle Cell death Cell Line, Tumor Cell migration Cell Proliferation Colorectal carcinoma Coordination Complexes - chemistry Doxorubicin Female Fibroblasts Humans Inorganic chemistry Life Sciences Manganese Microbiology Original Paper Ovarian carcinoma Ovarian Neoplasms - pathology Ovaries Reactive oxygen species Regenerative medicine Toxicity Tumor cell lines Tumors Vascularization Zebrafish |
| title | Manganese(I) tricarbonyl complexes as potential anticancer agents |
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