BIOMAT Database Logo BIOMAT Database Logo

[1,2,4]Triazolo[1,5-c]pyrimidines as Tools to Investigate A3 Adenosine Receptors in Cancer Cell Lines. 2023

Stephanie Federico, and Margherita Persico, and Letizia Trevisan, and Chiara Biasinutto, and Giovanni Bolcato, and Veronica Salmaso, and Tatiana Da Ros, and Teresa Gianferrara, and Filippo Prencipe, and Sonja Kachler, and Karl-Norbert Klotz, and Sabrina Pacor, and Stefano Moro, and Giampiero Spalluto
Department of Chemical and Pharmaceutical Sciences, University of Trieste, Via Licio Giorgieri 1, 34127, Trieste, Italy.

The A3 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.

UI MeSH Term Description Entries
D009369 Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D011743 Pyrimidines A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D006224 Cricetinae A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS. Cricetus,Hamsters,Hamster
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D016466 CHO Cells CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells. CHO Cell,Cell, CHO,Cells, CHO
D043684 Receptor, Adenosine A3 A subtype of ADENOSINE RECEPTOR that is found expressed in a variety of locations including the BRAIN and endocrine tissues. The receptor is generally considered to be coupled to the GI, INHIBITORY G-PROTEIN which causes down regulation of CYCLIC AMP. Adenosine A3 Receptors,Adenosine A3 Receptor,A3 Receptor, Adenosine,A3 Receptors, Adenosine,Receptors, Adenosine A3
D043705 Receptor, Adenosine A2A A subclass of adenosine A2 receptors found in LEUKOCYTES, the SPLEEN, the THYMUS and a variety of other tissues. It is generally considered to be a receptor for ADENOSINE that couples to the GS, STIMULATORY G-PROTEIN. Adenosine A2A Receptor,Adenosine A(2A) Receptor,Adenosine A2A Receptors,A2A Receptor, Adenosine,A2A Receptors, Adenosine,Receptors, Adenosine A2A
D058915 Purinergic P1 Receptor Antagonists Compounds that bind to and block the stimulation of PURINERGIC P1 RECEPTORS. Adenosine Receptor Antagonist,P1 Purinoceptor Antagonist,Purinergic P1 Receptor Antagonist,Adenosine Receptor Antagonists,P1 Purinoceptor Antagonists,Antagonist, Adenosine Receptor,Antagonist, P1 Purinoceptor,Antagonists, Adenosine Receptor,Antagonists, P1 Purinoceptor,Purinoceptor Antagonist, P1,Purinoceptor Antagonists, P1,Receptor Antagonist, Adenosine,Receptor Antagonists, Adenosine

Related Publications

Stephanie Federico, and Margherita Persico, and Letizia Trevisan, and Chiara Biasinutto, and Giovanni Bolcato, and Veronica Salmaso, and Tatiana Da Ros, and Teresa Gianferrara, and Filippo Prencipe, and Sonja Kachler, and Karl-Norbert Klotz, and Sabrina Pacor, and Stefano Moro, and Giampiero Spalluto
Pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine ligands, new tools to characterize A3 adenosine receptors in human tumor cell lines.
January 2005, Current medicinal chemistry,
Stephanie Federico, and Margherita Persico, and Letizia Trevisan, and Chiara Biasinutto, and Giovanni Bolcato, and Veronica Salmaso, and Tatiana Da Ros, and Teresa Gianferrara, and Filippo Prencipe, and Sonja Kachler, and Karl-Norbert Klotz, and Sabrina Pacor, and Stefano Moro, and Giampiero Spalluto
[1,2,4]Triazolo[1,5-c]pyrimidines as adenosine receptor antagonists: Modifications at the 8 position to reach selectivity towards A3 adenosine receptor subtype.
September 2018, European journal of medicinal chemistry,
Stephanie Federico, and Margherita Persico, and Letizia Trevisan, and Chiara Biasinutto, and Giovanni Bolcato, and Veronica Salmaso, and Tatiana Da Ros, and Teresa Gianferrara, and Filippo Prencipe, and Sonja Kachler, and Karl-Norbert Klotz, and Sabrina Pacor, and Stefano Moro, and Giampiero Spalluto
Pyrrolo- and pyrazolo-[3,4-e][1,2,4]triazolo[1,5-c]pyrimidines as adenosine receptor antagonists.
January 2012, Bioorganic & medicinal chemistry,
Stephanie Federico, and Margherita Persico, and Letizia Trevisan, and Chiara Biasinutto, and Giovanni Bolcato, and Veronica Salmaso, and Tatiana Da Ros, and Teresa Gianferrara, and Filippo Prencipe, and Sonja Kachler, and Karl-Norbert Klotz, and Sabrina Pacor, and Stefano Moro, and Giampiero Spalluto
Potent and selective adenosine A2A receptor antagonists: 1,2,4-Triazolo[1,5-c]pyrimidines.
February 2009, Bioorganic & medicinal chemistry letters,
Stephanie Federico, and Margherita Persico, and Letizia Trevisan, and Chiara Biasinutto, and Giovanni Bolcato, and Veronica Salmaso, and Tatiana Da Ros, and Teresa Gianferrara, and Filippo Prencipe, and Sonja Kachler, and Karl-Norbert Klotz, and Sabrina Pacor, and Stefano Moro, and Giampiero Spalluto
Pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidines to develop functionalized ligands to target adenosine receptors: fluorescent ligands as an example.
July 2019, MedChemComm,
Stephanie Federico, and Margherita Persico, and Letizia Trevisan, and Chiara Biasinutto, and Giovanni Bolcato, and Veronica Salmaso, and Tatiana Da Ros, and Teresa Gianferrara, and Filippo Prencipe, and Sonja Kachler, and Karl-Norbert Klotz, and Sabrina Pacor, and Stefano Moro, and Giampiero Spalluto
Water-soluble pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidines as human A₃ adenosine receptor antagonists.
June 2012, Journal of medicinal chemistry,
Stephanie Federico, and Margherita Persico, and Letizia Trevisan, and Chiara Biasinutto, and Giovanni Bolcato, and Veronica Salmaso, and Tatiana Da Ros, and Teresa Gianferrara, and Filippo Prencipe, and Sonja Kachler, and Karl-Norbert Klotz, and Sabrina Pacor, and Stefano Moro, and Giampiero Spalluto
Design, synthesis, and biological evaluation of C9- and C2-substituted pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines as new A2A and A3 adenosine receptors antagonists.
March 2003, Journal of medicinal chemistry,
Stephanie Federico, and Margherita Persico, and Letizia Trevisan, and Chiara Biasinutto, and Giovanni Bolcato, and Veronica Salmaso, and Tatiana Da Ros, and Teresa Gianferrara, and Filippo Prencipe, and Sonja Kachler, and Karl-Norbert Klotz, and Sabrina Pacor, and Stefano Moro, and Giampiero Spalluto
Facile synthesis of fused 1,2,4-triazolo[1,5-c]pyrimidine derivatives as human adenosine A3 receptor ligands.
May 2004, Bioorganic & medicinal chemistry letters,
Stephanie Federico, and Margherita Persico, and Letizia Trevisan, and Chiara Biasinutto, and Giovanni Bolcato, and Veronica Salmaso, and Tatiana Da Ros, and Teresa Gianferrara, and Filippo Prencipe, and Sonja Kachler, and Karl-Norbert Klotz, and Sabrina Pacor, and Stefano Moro, and Giampiero Spalluto
1,2,4-Triazolo[1,5-a]pyrimidines in drug design.
March 2019, European journal of medicinal chemistry,
Stephanie Federico, and Margherita Persico, and Letizia Trevisan, and Chiara Biasinutto, and Giovanni Bolcato, and Veronica Salmaso, and Tatiana Da Ros, and Teresa Gianferrara, and Filippo Prencipe, and Sonja Kachler, and Karl-Norbert Klotz, and Sabrina Pacor, and Stefano Moro, and Giampiero Spalluto
5,7-Disubstituted-[1,2,4]triazolo[1,5-a][1,3,5]triazines as pharmacological tools to explore the antagonist selectivity profiles toward adenosine receptors.
January 2016, European journal of medicinal chemistry,
Copied contents to your clipboard!