Natural product–drug conjugates for modulation of TRPV1-expressing tumors
| Autor: | Bernardo P. de Almeida, Gonçalo J. L. Bernardes, Charlotte Baker, Nuno L. Barbosa-Morais, Tiago Rodrigues |
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| Rok vydání: | 2019 |
| Předmět: |
Agonist
medicine.drug_class Cell Survival Clinical Biochemistry Chemical biology Pharmaceutical Science Gene Expression TRPV Cation Channels Antineoplastic Agents Ligands Biochemistry Small Molecule Libraries 03 medical and health sciences chemistry.chemical_compound Prostate cancer 0302 clinical medicine Prostate Cell Line Tumor Drug Discovery medicine Temozolomide Humans Molecular Biology 030304 developmental biology 0303 health sciences Biological Products Natural product Organic Chemistry Cancer medicine.disease 3. Good health medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis Drug delivery Cancer research Molecular Medicine Bioorthogonal chemistry Capsaicin |
| Zdroj: | Bioorganic & Medicinal Chemistry |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2019.03.025 |
| Popis: | We report the design, synthesis and biological evaluation of natural product-drug conjugates for treatment of prostate cancers over-expressing the transient receptor potential vanilloid 1 (TRPV1) channel. We validate the relevance of TRPV1 as a target in prostate cancer patients by using a bioinformatics approach and provide proof-of-concept for the drug delivery strategy through bioorthogonal chemistry and stability assays under simulated physiological conditions. In cell-based assays, the constructs displayed modest activity. Moreover, we serendipitously discover that a stoichiometric combination of a TRPV1 agonist with a small, positively charged cytotoxic may provide new research avenues in personalized medicines for prostate cancer. |
| Databáze: | OpenAIRE |
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