On the stability and biological behavior of cyclometallated Pt(IV) complexes with halido and aryl ligands in the axial positions
A series of cyclometallated platinum(IV) compounds (3a, 3a' and 3b') with a meridional [C,N,N'] terdentate ligand, featuring an halido and an aryl group in the axial positions has been evaluated for electrochemical reduction and preliminary biological behavior against a panel of human adenocarcinoma...
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| Format: | Article |
| Status: | Accepted version |
| Publication date: | 2016 |
| Country: | España |
| Institution: | Universidad de Barcelona |
| Repository: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/165158 |
| Online Access: | https://hdl.handle.net/2445/165158 |
| Access Level: | Open access |
| Keyword: | Platí Medicaments antineoplàstics Platinum Antineoplastic agents |
| _version_ | 1878733482361880576 |
|---|---|
| author | Escolà Jané, Anna |
| author2 | Crespo Vicente, Margarita Ma. López Martínez, Ma. Concepción Quirante Serrano, Josefina Jayaraman, Anusha Halil Polat, Ibrahim Badía Palacín, Josefa Baldomà Llavinés, Laura Cascante i Serratosa, Marta |
| author2_role | author author author author author author author author |
| author_browse | Badía Palacín, Josefa Baldomà Llavinés, Laura Cascante i Serratosa, Marta Crespo Vicente, Margarita Ma. Escolà Jané, Anna Halil Polat, Ibrahim Jayaraman, Anusha López Martínez, Ma. Concepción Quirante Serrano, Josefina |
| author_facet | Escolà Jané, Anna Crespo Vicente, Margarita Ma. López Martínez, Ma. Concepción Quirante Serrano, Josefina Jayaraman, Anusha Halil Polat, Ibrahim Badía Palacín, Josefa Baldomà Llavinés, Laura Cascante i Serratosa, Marta |
| author_role | author |
| collection | Dipòsit Digital de la UB |
| description | A series of cyclometallated platinum(IV) compounds (3a, 3a' and 3b') with a meridional [C,N,N'] terdentate ligand, featuring an halido and an aryl group in the axial positions has been evaluated for electrochemical reduction and preliminary biological behavior against a panel of human adenocarcinoma (A-549 lung, HCT-116 colon, and MCF-7 breast) cell lines and the normal bronquial epithelial BEAS-2B cells. Cathodic reduction potentials (shifting from -1.463 to -1.570 V) reveal that the platinum(IV) compounds under study would be highly reluctant to be reduced in a biological environment. Actually ascorbic acid was not able to reduce complex 3a', the most prone to be reduced according its reduction potential, over a period of one week. These results suggest an intrinsic activity for the investigated platinum(IV) complexes (3a, 3a' and 3b'), which exhibit a remarkable cytotoxicity effectiveness (with IC50 values in the low micromolar range), even greater than that of cisplatin. The IC50 for A-549 lung cells and clog P values were found to follow the same trend: 3b' > 3a' > 3a. However, no correlation was observed between reduction potential and in vitro activity. As a representative example, cyclometallated platinum(IV) compound 3a', exercise its antiproliferative activity directly over non-microcytic A-549 lung cancer cells through a mixture of cell cycle arrest (13% arrest at G1 phase and 46% arrest at G2 phase) and apoptosis induction (increase of early apoptosis by 30 times with regard to control). To gain further insights into the mode of action of the investigated platinum(IV) complexes, drug uptake, cathepsin B inhibition and ROS generation were also evaluated. Interestingly an increased ROS generation could be related with the antiproliferative activity of the cyclometallated platinum(IV) series under study in the cisplatin-resistant A-549 lung and HCT-116 cancer cell lines. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_56fd00a95a46786d31e70d34d7d5058a |
| institution | Universidad de Barcelona |
| instname_str | Universidad de Barcelona |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:diposit.ub.edu:2445/165158 |
| publishDate | 2016 |
| publishDateSort | 2016 |
| publisher | Elsevier Ltd |
| publisherStr | Elsevier Ltd |
| reponame_str | Dipòsit Digital de la UB |
| spelling | On the stability and biological behavior of cyclometallated Pt(IV) complexes with halido and aryl ligands in the axial positions Escolà Jané, Anna Crespo Vicente, Margarita Ma. López Martínez, Ma. Concepción Quirante Serrano, Josefina Jayaraman, Anusha Halil Polat, Ibrahim Badía Palacín, Josefa Baldomà Llavinés, Laura Cascante i Serratosa, Marta Platí Medicaments antineoplàstics Platinum Antineoplastic agents A series of cyclometallated platinum(IV) compounds (3a, 3a' and 3b') with a meridional [C,N,N'] terdentate ligand, featuring an halido and an aryl group in the axial positions has been evaluated for electrochemical reduction and preliminary biological behavior against a panel of human adenocarcinoma (A-549 lung, HCT-116 colon, and MCF-7 breast) cell lines and the normal bronquial epithelial BEAS-2B cells. Cathodic reduction potentials (shifting from -1.463 to -1.570 V) reveal that the platinum(IV) compounds under study would be highly reluctant to be reduced in a biological environment. Actually ascorbic acid was not able to reduce complex 3a', the most prone to be reduced according its reduction potential, over a period of one week. These results suggest an intrinsic activity for the investigated platinum(IV) complexes (3a, 3a' and 3b'), which exhibit a remarkable cytotoxicity effectiveness (with IC50 values in the low micromolar range), even greater than that of cisplatin. The IC50 for A-549 lung cells and clog P values were found to follow the same trend: 3b' > 3a' > 3a. However, no correlation was observed between reduction potential and in vitro activity. As a representative example, cyclometallated platinum(IV) compound 3a', exercise its antiproliferative activity directly over non-microcytic A-549 lung cancer cells through a mixture of cell cycle arrest (13% arrest at G1 phase and 46% arrest at G2 phase) and apoptosis induction (increase of early apoptosis by 30 times with regard to control). To gain further insights into the mode of action of the investigated platinum(IV) complexes, drug uptake, cathepsin B inhibition and ROS generation were also evaluated. Interestingly an increased ROS generation could be related with the antiproliferative activity of the cyclometallated platinum(IV) series under study in the cisplatin-resistant A-549 lung and HCT-116 cancer cell lines. Elsevier Ltd https://hdl.handle.net/2445/165158 |
| spellingShingle | On the stability and biological behavior of cyclometallated Pt(IV) complexes with halido and aryl ligands in the axial positions Escolà Jané, Anna Platí Medicaments antineoplàstics Platinum Antineoplastic agents |
| status_str | acceptedVersion |
| title | On the stability and biological behavior of cyclometallated Pt(IV) complexes with halido and aryl ligands in the axial positions |
| title_full | On the stability and biological behavior of cyclometallated Pt(IV) complexes with halido and aryl ligands in the axial positions |
| title_fullStr | On the stability and biological behavior of cyclometallated Pt(IV) complexes with halido and aryl ligands in the axial positions |
| title_full_unstemmed | On the stability and biological behavior of cyclometallated Pt(IV) complexes with halido and aryl ligands in the axial positions |
| title_short | On the stability and biological behavior of cyclometallated Pt(IV) complexes with halido and aryl ligands in the axial positions |
| title_sort | On the stability and biological behavior of cyclometallated Pt(IV) complexes with halido and aryl ligands in the axial positions |
| topic | Platí Medicaments antineoplàstics Platinum Antineoplastic agents |
| topic_facet | Platí Medicaments antineoplàstics Platinum Antineoplastic agents |
| url | https://hdl.handle.net/2445/165158 |