Theoretical Prediction of Dual-Potency Anti-Tumor Agents: Combination of Oxoplatin with Other FDA-Approved Oncology Drugs.
Jose Pedro Cerón-CarrascoPublished in: International journal of molecular sciences (2020)
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.
Keyphrases
- drug administration
- palliative care
- healthcare
- public health
- machine learning
- drug induced
- cancer therapy
- photodynamic therapy
- mental health
- single cell
- molecular dynamics
- stem cells
- papillary thyroid
- hydrogen peroxide
- minimally invasive
- molecular dynamics simulations
- emergency department
- cell therapy
- oxidative stress
- drug delivery
- health promotion
- squamous cell
- lymph node metastasis
- locally advanced
- metal organic framework