Natural product-drug conjugates for modulation of TRPV1-expressing tumors.
de Almeida, Bernardo P
Bioorganic & medicinal chemistry
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Baker, C., Rodrigues, T., de Almeida, B. P., Barbosa-Morais, N. L., & Lopes Bernardes, G. (2019). Natural product-drug conjugates for modulation of TRPV1-expressing tumors.. Bioorganic & medicinal chemistry, 27 (12), 2531-2536. https://doi.org/10.1016/j.bmc.2019.03.025
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 select 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.
Cell Line, Tumor, Humans, Capsaicin, Antineoplastic Agents, Biological Products, Ligands, Cell Survival, Gene Expression, TRPV Cation Channels, Small Molecule Libraries, Temozolomide
Royal Society (URF\R\180019)
Royal Society (uf110046)
European Commission Horizon 2020 (H2020) ERC (676832)
European Commission Horizon 2020 (H2020) Spreading Excellence and Widening Participation (807281)
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (675007)
External DOI: https://doi.org/10.1016/j.bmc.2019.03.025
This record's URL: https://www.repository.cam.ac.uk/handle/1810/290583
Attribution-NonCommercial-NoDerivatives 4.0 International
Licence URL: https://creativecommons.org/licenses/by-nc-nd/4.0/