1312766-21-4Relevant articles and documents
3-(Fur-2-yl)-10-(2-phenylethyl)-[1,2,4]triazino[4,3-a]benzimidazol-4(10H)- one, a novel adenosine receptor antagonist with A2A-mediated neuroprotective effects
Scatena, Alessia,Fornai, Francesco,Trincavelli, Maria Letizia,Taliani, Sabrina,Daniele, Simona,Pugliesi, Isabella,Cosconati, Sandro,Martini, Claudia,Da Settimo, Federico
, p. 526 - 535 (2015/03/03)
In this study, compound FTBI (3-(2-furyl)-10-(2-phenylethyl)[1,2,4]triazino[4,3-a]benzimidazol-4(10H)-one) was selected from a small library of triazinobenzimidazole derivatives as a potent A2Aadenosine receptor (AR) antagonist and tested for its neuroprotective effects against two different kinds of dopaminergic neurotoxins, 1-methyl-4-phenylpyridinium (MPP+) and methamphetamine (METH), in rat PC12 and in human neuroblastoma SH-SY5Y cell lines. FTBI, in a concentration range corresponding to its affinity for A2AAR subtype, significantly increased the number of viable PC12 cells after their exposure to METHand, to a similar extent, to MPP+, as demonstrated in both trypan blue exclusion assay and in cytological staining. These neuroprotective effects were also observed with a classical A2AAR antagonist, ZM241385, and appeared to be completely counteracted by the AR agonist, NECA, supporting A2AARs are directly involved in FTBI-mediated effects. Similarly, in human SH-SY5Y cells, FTBI was able to prevent cell toxicity induced by MPP+ and METH, showing that this A2AAR antagonist has a neuroprotective effect independently by the specific cell model. Altogether these results demonstrate that the A2AAR blockade mediates cell protection against neurotoxicity induced by dopaminergic neurotoxins in dopamine containing cells, supporting the potential use of A2AAR antagonists in dopaminergic degenerative diseases including Parkinson's disease.
3-Aryl-[1,2,4]triazino[4,3-a ]benzimidazol-4(10 H)-one: A novel template for the design of highly selective A2B adenosine receptor antagonists
Taliani, Sabrina,Pugliesi, Isabella,Barresi, Elisabetta,Simorini, Francesca,Salerno, Silvia,La Motta, Concettina,Marini, Anna Maria,Cosimelli, Barbara,Cosconati, Sandro,Di Maro, Salvatore,Marinelli, Luciana,Daniele, Simona,Trincavelli, Maria Letizia,Greco, Giovanni,Novellino, Ettore,Martini, Claudia,Da Settimo, Federico
, p. 1490 - 1499 (2012/04/23)
In an effort to identify novel ligands possessing high affinity and selectivity for the A2B AR subtype, we further investigated the class of 3-aryl[1,2,4]triazino[4,3-a]benzimidazol-4(10H)-ones V, previously disclosed by us as selective A1 AR antagonists. Preliminary assays on a number of triazinobenzimidazoles derived from our "in-house" collection revealed that all the derivatives selected showed significant affinity at A 2B AR, no affinity at A3 AR, and various degrees of selectivity toward A1 and A2A ARs. Investigation of a new series featuring modified substituents at the 10-position (4′-chlorophenyl or phenylethyl groups), and a chlorine atom at the 7-position (X) of the triazinobenzimidazole nucleus, yielded highly potent and selective A 2B AR antagonists. The presence of a pendant 3-phenyl ring appears to hamper the interaction with A2A AR, conferring high A 2B/A2A AR selectivity. Derivative 13 (X = Cl, R = C 6H5) is the most potent and selective compound, with an IC50 of 3.10 nM at A2B AR and no affinity at A 1, A2A, and A3 ARs.
