Theoretical Prediction of Dual-Potency Anti-Tumor Agents: Combination of Oxoplatin with Other FDA-Approved Oncology Drugs
Although Pt(II)-based drugs are widely used to treat cancer, very few molecules have been approved for routine use in chemotherapy due to their side-effects on healthy tissues. A new approach to reducing the toxicity of these drugs is generating a prodrug by increasing the oxidation state of the met...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/13/4741 |
| _version_ | 1797563354114424832 |
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| author | José Pedro Cerón-Carrasco |
| author_facet | José Pedro Cerón-Carrasco |
| author_sort | José Pedro Cerón-Carrasco |
| collection | DOAJ |
| description | Although Pt(II)-based drugs are widely used to treat cancer, very few molecules have been approved for routine use in chemotherapy due to their side-effects on healthy tissues. A new approach to reducing the toxicity of these drugs is generating a prodrug by increasing the oxidation state of the metallic center to Pt(IV), a less reactive form that is only activated once it enters a cell. We used theoretical tools to combine the parent Pt(IV) prodrug, oxoplatin, with the most recent FDA-approved anti-cancer drug set published by the National Institute of Health (NIH). The only prerequisite imposed for the latter was the presence of one carboxylic group in the structure, a chemical feature that ensures a link to the coordination sphere via a simple esterification procedure. Our calculations led to a series of bifunctional prodrugs ranked according to their relative stabilities and activation profiles. Of all the designed molecules, the combination of oxoplatin with aminolevulinic acid as the bioactive ligand emerged as the most promising strategy by which to design enhanced dual-potency oncology drugs. |
| first_indexed | 2024-03-10T18:42:26Z |
| format | Article |
| id | doaj.art-505c3c7c942f42f185a46aa7c06c006f |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T18:42:26Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-505c3c7c942f42f185a46aa7c06c006f2023-11-20T05:44:37ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-07-012113474110.3390/ijms21134741Theoretical Prediction of Dual-Potency Anti-Tumor Agents: Combination of Oxoplatin with Other FDA-Approved Oncology DrugsJosé Pedro Cerón-Carrasco0Reconocimiento y Encapsulación Molecular, Universidad Católica San Antonio de Murcia Campus los Jerónimos, 30107 Murcia, SpainAlthough Pt(II)-based drugs are widely used to treat cancer, very few molecules have been approved for routine use in chemotherapy due to their side-effects on healthy tissues. A new approach to reducing the toxicity of these drugs is generating a prodrug by increasing the oxidation state of the metallic center to Pt(IV), a less reactive form that is only activated once it enters a cell. We used theoretical tools to combine the parent Pt(IV) prodrug, oxoplatin, with the most recent FDA-approved anti-cancer drug set published by the National Institute of Health (NIH). The only prerequisite imposed for the latter was the presence of one carboxylic group in the structure, a chemical feature that ensures a link to the coordination sphere via a simple esterification procedure. Our calculations led to a series of bifunctional prodrugs ranked according to their relative stabilities and activation profiles. Of all the designed molecules, the combination of oxoplatin with aminolevulinic acid as the bioactive ligand emerged as the most promising strategy by which to design enhanced dual-potency oncology drugs.https://www.mdpi.com/1422-0067/21/13/4741cancerdrug designorganometallicsplatinum-based drugsbifunctional compoundstheoretical tools |
| spellingShingle | José Pedro Cerón-Carrasco Theoretical Prediction of Dual-Potency Anti-Tumor Agents: Combination of Oxoplatin with Other FDA-Approved Oncology Drugs International Journal of Molecular Sciences cancer drug design organometallics platinum-based drugs bifunctional compounds theoretical tools |
| title | Theoretical Prediction of Dual-Potency Anti-Tumor Agents: Combination of Oxoplatin with Other FDA-Approved Oncology Drugs |
| title_full | Theoretical Prediction of Dual-Potency Anti-Tumor Agents: Combination of Oxoplatin with Other FDA-Approved Oncology Drugs |
| title_fullStr | Theoretical Prediction of Dual-Potency Anti-Tumor Agents: Combination of Oxoplatin with Other FDA-Approved Oncology Drugs |
| title_full_unstemmed | Theoretical Prediction of Dual-Potency Anti-Tumor Agents: Combination of Oxoplatin with Other FDA-Approved Oncology Drugs |
| title_short | Theoretical Prediction of Dual-Potency Anti-Tumor Agents: Combination of Oxoplatin with Other FDA-Approved Oncology Drugs |
| title_sort | theoretical prediction of dual potency anti tumor agents combination of oxoplatin with other fda approved oncology drugs |
| topic | cancer drug design organometallics platinum-based drugs bifunctional compounds theoretical tools |
| url | https://www.mdpi.com/1422-0067/21/13/4741 |
| work_keys_str_mv | AT josepedroceroncarrasco theoreticalpredictionofdualpotencyantitumoragentscombinationofoxoplatinwithotherfdaapprovedoncologydrugs |