Recent Advances in Light-Controlled Activation of Pt(IV) Prodrugs
Pt(IV) prodrugs remain one of the most promising alternatives to conventional Pt(II) therapy due to their versatility in axial ligand choice and delayed mode of action. Selective activation from an external source is especially attractive due to the opportunity to control the activity of an antitumo...
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| Veröffentlicht in: | International journal of molecular sciences 2022-11, Vol.23 (23), p.14511 |
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| creator | Spector, Daniil Pavlov, Kirill Beloglazkina, Elena Krasnovskaya, Olga |
| description | Pt(IV) prodrugs remain one of the most promising alternatives to conventional Pt(II) therapy due to their versatility in axial ligand choice and delayed mode of action. Selective activation from an external source is especially attractive due to the opportunity to control the activity of an antitumor drug in space and time and avoid damage to normal tissues. In this review, we discuss recent advances in photoabsorber-mediated photocontrollable activation of Pt(IV) prodrugs. Two main approaches developed are the focus of the review. The first one is the photocatalytic strategy based on the flavin derivatives that are not covalently bound to the Pt(IV) substrate. The second one is the conjugation of photoactive molecules with the Pt(II) drug via axial position, yielding dual-action Pt(IV) molecules capable of the controllable release of Pt(II) cytotoxic agents. Thus, Pt(IV) prodrugs with a light-controlled mode of activation are non-toxic in the absence of light, but show high antiproliferative activity when irradiated. The susceptibility of Pt(IV) prodrugs to photoreduction, photoactivation mechanisms, and biological activity is considered in this review. |
| doi_str_mv | 10.3390/ijms232314511 |
| format | Article |
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Selective activation from an external source is especially attractive due to the opportunity to control the activity of an antitumor drug in space and time and avoid damage to normal tissues. In this review, we discuss recent advances in photoabsorber-mediated photocontrollable activation of Pt(IV) prodrugs. Two main approaches developed are the focus of the review. The first one is the photocatalytic strategy based on the flavin derivatives that are not covalently bound to the Pt(IV) substrate. The second one is the conjugation of photoactive molecules with the Pt(II) drug via axial position, yielding dual-action Pt(IV) molecules capable of the controllable release of Pt(II) cytotoxic agents. Thus, Pt(IV) prodrugs with a light-controlled mode of activation are non-toxic in the absence of light, but show high antiproliferative activity when irradiated. The susceptibility of Pt(IV) prodrugs to photoreduction, photoactivation mechanisms, and biological activity is considered in this review.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms232314511</identifier><identifier>PMID: 36498837</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Antineoplastic Agents - therapeutic use ; Apoptosis ; Biological activity ; Cancer therapies ; Cell Line, Tumor ; Chemotherapy ; Conjugation ; Controllability ; Cytotoxic agents ; Cytotoxicity ; Drug dosages ; Drugs ; Flavin ; Investigations ; Ligands ; Light ; Metabolism ; Photoactivation ; Photocatalysis ; Photoreduction ; Prodrugs ; Prodrugs - chemistry ; Prostate cancer ; Review ; Reviews ; Toxicity ; Vitamin B</subject><ispartof>International journal of molecular sciences, 2022-11, Vol.23 (23), p.14511</ispartof><rights>2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). 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Selective activation from an external source is especially attractive due to the opportunity to control the activity of an antitumor drug in space and time and avoid damage to normal tissues. In this review, we discuss recent advances in photoabsorber-mediated photocontrollable activation of Pt(IV) prodrugs. Two main approaches developed are the focus of the review. The first one is the photocatalytic strategy based on the flavin derivatives that are not covalently bound to the Pt(IV) substrate. The second one is the conjugation of photoactive molecules with the Pt(II) drug via axial position, yielding dual-action Pt(IV) molecules capable of the controllable release of Pt(II) cytotoxic agents. Thus, Pt(IV) prodrugs with a light-controlled mode of activation are non-toxic in the absence of light, but show high antiproliferative activity when irradiated. The susceptibility of Pt(IV) prodrugs to photoreduction, photoactivation mechanisms, and biological activity is considered in this review.</description><subject>Antineoplastic Agents - therapeutic use</subject><subject>Apoptosis</subject><subject>Biological activity</subject><subject>Cancer therapies</subject><subject>Cell Line, Tumor</subject><subject>Chemotherapy</subject><subject>Conjugation</subject><subject>Controllability</subject><subject>Cytotoxic agents</subject><subject>Cytotoxicity</subject><subject>Drug dosages</subject><subject>Drugs</subject><subject>Flavin</subject><subject>Investigations</subject><subject>Ligands</subject><subject>Light</subject><subject>Metabolism</subject><subject>Photoactivation</subject><subject>Photocatalysis</subject><subject>Photoreduction</subject><subject>Prodrugs</subject><subject>Prodrugs - chemistry</subject><subject>Prostate cancer</subject><subject>Review</subject><subject>Reviews</subject><subject>Toxicity</subject><subject>Vitamin B</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkd1LwzAUxYMobk4ffZWCL_OhmjRJk7wIZfgxGDhEfQ1pmm4ZXTOTduB_b8fm2Hy6F-6Pc8_hAHCN4D3GAj7YxTIkOMGIUIROQB-RJIkhTNnpwd4DFyEsIOxAKs5BD6dEcI5ZH2TvRpu6ibJirWptQmTraGJn8yYeubrxrqpMEWW6sWvVWFdHroymzXD8dRdNvSt8OwuX4KxUVTBXuzkAn89PH6PXePL2Mh5lk1gTRJtY5Z1DqKChuYGUpgUUIhGKsFwYorASyGiOMUNCU86FMpxqnbKSYcJRahgegMet7qrNl6bYuPaqkitvl8r_SKesPL7Udi5nbi0Fw4IJ1AkMdwLefbcmNHJpgzZVpWrj2iATRjGGSfe8Q2__oQvX-rqL11GEU8Ih3lDxltLeheBNuTeDoNyUI4_K6fibwwR7-q8N_Avrg4l0</recordid><startdate>20221122</startdate><enddate>20221122</enddate><creator>Spector, Daniil</creator><creator>Pavlov, Kirill</creator><creator>Beloglazkina, Elena</creator><creator>Krasnovskaya, Olga</creator><general>MDPI AG</general><general>MDPI</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-2726-2671</orcidid><orcidid>https://orcid.org/0000-0001-9824-8300</orcidid><orcidid>https://orcid.org/0000-0001-6796-8241</orcidid><orcidid>https://orcid.org/0000-0002-4948-2747</orcidid></search><sort><creationdate>20221122</creationdate><title>Recent Advances in Light-Controlled Activation of Pt(IV) Prodrugs</title><author>Spector, Daniil ; 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Selective activation from an external source is especially attractive due to the opportunity to control the activity of an antitumor drug in space and time and avoid damage to normal tissues. In this review, we discuss recent advances in photoabsorber-mediated photocontrollable activation of Pt(IV) prodrugs. Two main approaches developed are the focus of the review. The first one is the photocatalytic strategy based on the flavin derivatives that are not covalently bound to the Pt(IV) substrate. The second one is the conjugation of photoactive molecules with the Pt(II) drug via axial position, yielding dual-action Pt(IV) molecules capable of the controllable release of Pt(II) cytotoxic agents. Thus, Pt(IV) prodrugs with a light-controlled mode of activation are non-toxic in the absence of light, but show high antiproliferative activity when irradiated. 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| subjects | Antineoplastic Agents - therapeutic use Apoptosis Biological activity Cancer therapies Cell Line, Tumor Chemotherapy Conjugation Controllability Cytotoxic agents Cytotoxicity Drug dosages Drugs Flavin Investigations Ligands Light Metabolism Photoactivation Photocatalysis Photoreduction Prodrugs Prodrugs - chemistry Prostate cancer Review Reviews Toxicity Vitamin B |
| title | Recent Advances in Light-Controlled Activation of Pt(IV) Prodrugs |
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