Natural product-drug conjugates for modulation of TRPV1-expressing tumors.


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Type
Article
Change log
Authors
Baker, Charlotte 
Rodrigues, Tiago 
de Almeida, Bernardo P 
Barbosa-Morais, Nuno L 
Bernardes, Gonçalo JL 
Abstract

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.

Description
Keywords
Cancer, Chemical biology, Drug delivery, Ligand-gated ion channel, Small molecule–drug conjugates, Antineoplastic Agents, Biological Products, Capsaicin, Cell Line, Tumor, Cell Survival, Gene Expression, Humans, Ligands, Small Molecule Libraries, TRPV Cation Channels, Temozolomide
Journal Title
Bioorg Med Chem
Conference Name
Journal ISSN
0968-0896
1464-3391
Volume Title
27
Publisher
Elsevier BV
Sponsorship
Royal Society (URF\R\180019)
The Royal Society (uf110046)
European Research Council (676832)
European Commission Horizon 2020 (H2020) Spreading Excellence and Widening Participation (807281)
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (675007)