Novel 8-amino-1,2,4-triazolo[4,3-a]pyrazin-3-one derivatives as potent human adenosine A1 and A2A receptor antagonists. Evaluation of their protective effect against β-amyloid-induced neurotoxicity in SH-SY5Y cells

Falsini, Matteo; Catarzi, Daniela; Varano, Flavia; Ben, Diego Dal; Marucci, Gabriella; Buccioni, Michela; Volpini, Rosaria; Mannelli, Lorenzo Di Cesare; Ghelardini, Carla; Colotta, Vittoria

doi:10.1016/j.bioorg.2019.03.046

Cited by 13 publications

(13 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A 2A receptor blockade also neuroprotects these cells against neurotoxicity induced by α-synuclein, which is involved in PD [41]. In addition, A 1 and A 2A receptors have been also involved in neuroprotection against β-amyloid peptide neurotoxicity, which is related to AD [38,40], and in the neuroprotective action evoked by fullerene nanoparticles against hypoxic insult [39].…”

Section: Discussionmentioning

confidence: 99%

“…Adenosine regulates neuroplasticity, cognitive and motor function, and emotion behaviors and it is related to many cerebral dysfunctions in human diseases [30,31]. Additionally, adenosine receptors function and level have been involved in neuroprotective and antitumoral mechanisms in C6 [32,33,34,35,36,37] and SH-SY5Y cells [32,38,39,40,41].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Modulation of Adenosine Receptors and Antioxidative Effect of Beer Extracts in in Vitro Models

2019

View full text Add to dashboard Cite

The fight against neurodegenerative diseases is promoting the searching of nutrients, preferably of wide consumption, with proven effects on health. Beer is widely consumed and has potential benefits on health. In this work, three different extracts from dark beer (DB), non-alcoholic beer (NAB), and lager beer (LB) were assayed at 30 min and 24 h in rat C6 glioma and human SH-SY5Y neuroblastoma cells in order to study their possible protective effects. Cell viability and adenosine A1, A2A, A2B, and A3 receptor gene expression and protein levels were measured in control cells and in cells challenged with hydrogen peroxide as an oxidant stressor. Among the three extracts analyzed, DB showed a greater protective effect against H2O2-induced oxidative stress and cell death. Moreover, a higher A1 receptor level was also induced by this extract. Interestingly, A1 receptor level was also increased by NAB and LB extracts, but to a lower extent, and the protective effect of these extracts against H2O2 was lower. This possible correlation between protection and A1 receptor level was observed at 24 h in both C6 and SH-SY5Y cells. In summary, different beer extracts modulate, to a different degree, adenosine receptors expression and protect both glioma and neuroblastoma cells from oxidative stress.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Modulation of Adenosine Receptors and Antioxidative Effect of Beer Extracts in in Vitro Models

2019

View full text Add to dashboard Cite

show abstract

“…Our efforts in the pursuit of novel AR antagonists have centered on mono- or bicyclic heteroaromatic systems. [ 26 , 27 , 28 , 29 , 30 ]. Within this research, an interesting class of antagonists/inverse agonists (i.e., the thiazolo[5,4-d]pyrimidine series) was identified [ 31 , 32 , 33 , 34 , 35 ].…”

Section: Introductionmentioning

confidence: 99%

Design and Synthesis of Novel Thiazolo[5,4-d]pyrimidine Derivatives with High Affinity for Both the Adenosine A1 and A2A Receptors, and Efficacy in Animal Models of Depression

et al. 2021

Self Cite

View full text Add to dashboard Cite

New compounds with a 7-amino-2-arylmethyl-thiazolo[5,4-d]pyrimidine structure were synthesized and evaluated in vitro for their affinity and/or potency at the human (h) A1, hA2A, hA2B, and hA3 adenosine receptors (ARs). Several compounds (5, 8–10, 13, 18, 19) were characterized by nanomolar and subnanomolar binding affinities for the hA1 and the hA2A AR, respectively. Results of molecular docking studies supported the in vitro results. The 2-(2-fluorobenzyl)-5-(furan-2yl)-thiazolo[5,4-d]pyrimidin-7-amine derivative 18 (hA1 Ki = 1.9 nM; hA2A Ki = 0.06 nM) was evaluated for its antidepressant-like activity in in vivo studies, the forced swimming test (FST), the tail suspension test (TST), and the sucrose preference test (SPT) in mice, showing an effect comparable to that of the reference amitriptyline.

show abstract

“…Indeed, four A2A AR antagonists, including Preladenant [17], PBF-509 [18], CPI-444 [19], and AZD4635 [20] have entered clinical development as anticancer drugs alone and in combination with other agents (Figure 1). Our group previously synthesized some potent human (h) A2A AR antagonists/inverse agonists belonging to different chemical classes [21][22][23][24][25][26][27][28][29][30][31]. Among these, the thiazolo [5,4-d]pyrimidine one (TP series) has been deeply investigated allowing us to delineate comprehensive structure activity relationships [21,[25][26][27]31].…”

Section: Introductionmentioning

confidence: 99%

“…Our group previously synthesized some potent human (h) A 2A AR antagonists/inverse agonists belonging to different chemical classes [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ]. Among these, the thiazolo[5,4- d ]pyrimidine one (TP series) has been deeply investigated allowing us to delineate comprehensive structure activity relationships [ 21 , 25 , 26 , 27 , 31 ].…”

Section: Introductionmentioning

confidence: 99%

Piperazine- and Piperidine-Containing Thiazolo[5,4-d]pyrimidine Derivatives as New Potent and Selective Adenosine A2A Receptor Inverse Agonists

et al. 2020

Self Cite

View full text Add to dashboard Cite

The therapeutic use of A2A adenosine receptor (AR) antagonists for the treatment of neurodegenerative disorders, such as Parkinson and Alzheimer diseases, is a very promising approach. Moreover, the potential therapeutic role of A2A AR antagonists to avoid both immunoescaping of tumor cells and tumor development is well documented. Herein, we report on the synthesis and biological evaluation of a new set of piperazine- and piperidine- containing 7-amino-2-(furan-2-yl)thiazolo[5,4-d]pyrimidine derivatives designed as human A2A AR antagonists/inverse agonists. Binding and potency data indicated that a good number of potent and selective hA2A AR inverse agonists were found. Amongst them, the 2-(furan-2-yl)-N5-(2-(4-phenylpiperazin-1-yl)ethyl)thiazolo[5,4-d]pyrimidine-5,7-diamine 11 exhibited the highest A2A AR binding affinity (Ki = 8.62 nM) as well as inverse agonist potency (IC50 = 7.42 nM). In addition, bioinformatics prediction using the web tool SwissADME revealed that 8, 11, and 19 possessed good drug-likeness profiles.

show abstract

Novel 8-amino-1,2,4-triazolo[4,3-a]pyrazin-3-one derivatives as potent human adenosine A1 and A2A receptor antagonists. Evaluation of their protective effect against β-amyloid-induced neurotoxicity in SH-SY5Y cells

Cited by 13 publications

References 40 publications

Modulation of Adenosine Receptors and Antioxidative Effect of Beer Extracts in in Vitro Models

Modulation of Adenosine Receptors and Antioxidative Effect of Beer Extracts in in Vitro Models

Design and Synthesis of Novel Thiazolo[5,4-d]pyrimidine Derivatives with High Affinity for Both the Adenosine A1 and A2A Receptors, and Efficacy in Animal Models of Depression

Piperazine- and Piperidine-Containing Thiazolo[5,4-d]pyrimidine Derivatives as New Potent and Selective Adenosine A2A Receptor Inverse Agonists

Contact Info

Product

Resources

About