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1.
Rep Prog Phys ; 85(2)2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-34942603

RESUMO

In this paper, we describe the potential of the LHCb experiment to detect stealth physics. This refers to dynamics beyond the standard model that would elude searches that focus on energetic objects or precision measurements of known processes. Stealth signatures include long-lived particles and light resonances that are produced very rarely or together with overwhelming backgrounds. We will discuss why LHCb is equipped to discover this kind of physics at the Large Hadron Collider and provide examples of well-motivated theoretical models that can be probed with great detail at the experiment.

2.
Bioorg Med Chem ; 27(8): 1449-1455, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30528164

RESUMO

Extracellular adenosine 5'-triphosphate (ATP) triggers the P2X7 receptor (P2X7R) ionic channel to stimulate the release of the interleukin-IL-1ß cytokine into macrophages. The current study explored the reaction of six structurally diverse triazole derivatives on P2X7-mediated dye uptake into murine peritoneal macrophages. P2X7R activity determined by ATP-evoked fluorescent dye uptake. Triazole derivatives toxicity measured using dextran rhodamine exclusion based colorimetric assay. A740004 and BBG, both P2X7R antagonist, inhibited ATP-induced dye uptake. In contrast, the derivatives 5a, 5b, 5e, and 5f did not diminish P2X7R activity in concentrations until 100 µM. 5c and 5d analogs caused a potent inhibitory activity on P2X7-induced dye uptake. Dextran Rhodamine exclusion measurements after 24 h of continuous treatment with triazole derivatives indicated a moderated toxicity for all molecules. In conclusion, this study showed that a series of new hybrid 1,2,3-triazolic naphthoquinones reduces P2X7R-induced dye uptake into murine macrophages. In silico analysis indicates a good pharmacokinetic profile and molecular docking results of these analogs indicate the potential to bind into an allosteric site located into the P2X7R pore and juxtaposed with the ATP binding pocket. In this manner, the compounds 5c and 5d may be used as a scaffold for new P2X7R inhibitors with reduced toxicity, and good anti-inflammatory activity.


Assuntos
Naftoquinonas/química , Antagonistas do Receptor Purinérgico P2X/química , Receptores Purinérgicos P2X7/metabolismo , Triazóis/química , Sítio Alostérico , Animais , Sítios de Ligação , Células CACO-2 , Linhagem Celular , Corantes/metabolismo , Humanos , Macrófagos/citologia , Macrófagos/metabolismo , Camundongos , Microssomos Hepáticos/metabolismo , Simulação de Acoplamento Molecular , Permeabilidade/efeitos dos fármacos , Estrutura Terciária de Proteína , Antagonistas do Receptor Purinérgico P2X/metabolismo , Antagonistas do Receptor Purinérgico P2X/farmacologia , Receptores Purinérgicos P2X7/química , Triazóis/metabolismo , Triazóis/farmacologia
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