1. [1,2,4]Triazolo[1,5-c]pyrimidines as Tools to Investigate A 3 Adenosine Receptors in Cancer Cell Lines.
- Author
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Federico S, Persico M, Trevisan L, Biasinutto C, Bolcato G, Salmaso V, Da Ros T, Gianferrara T, Prencipe F, Kachler S, Klotz KN, Pacor S, Moro S, and Spalluto G
- Subjects
- Cricetinae, Animals, Structure-Activity Relationship, Receptors, Purinergic P1 chemistry, Receptors, Purinergic P1 metabolism, Cell Line, Pyrimidines chemistry, Purinergic P1 Receptor Antagonists pharmacology, Purinergic P1 Receptor Antagonists chemistry, CHO Cells, Receptor, Adenosine A2A, Receptor, Adenosine A3 metabolism, Neoplasms
- Abstract
The A
3 adenosine receptor is an interesting target whose role in cancer is controversial. In this work, a structural investigation at the 2-position of the [1,2,4]triazolo[1,5-c]pyrimidine nucleus was performed, finding new potent and selective A3 adenosine receptor antagonists such as the ethyl 2-(4-methoxyphenyl)-5-(methylamino)-[1,2,4]triazolo[1,5-c]pyrimidine-8-carboxylate (20, DZ123) that showed a Ki value of 0.47 nM and an exceptional selectivity profile over the other adenosine receptor subtypes. Computational studies were performed to rationalize the affinity and the selectivity profile of the tested compounds at the A3 adenosine receptor and the A1 and A2A adenosine receptors. Compound 20 was tested on both A3 adenosine receptor positive cell lines (CHO-A3 AR transfected, THP1 and HCT16) and on A3 negative cancer cell lines, showing no effect in the latter and a pro-proliferative effect at a low concentration in the former. These interesting results pave the way to further investigation on both the mechanism involved and potential therapeutic applications., (© 2023 Wiley-VCH GmbH.)- Published
- 2023
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