Synthesis, biological evaluation and molecular modeling studies of novel 1,2,3-triazole-linked menadione-furan derivatives as P2X7 inhibitors.

Autor: Dos Santos JPS; Laboratory of Studies in Experimental Pharmacology, Biomedical Science Institute, Universidade Federal Do Rio de Janeiro, Rio de Janeiro, RJ, Brazil., Ribeiro RCB; Departamento de Química Orgânica, Instituto de Química, Universidade Federal Fluminense, Campus do Valonguinho, Niterói, RJ, 24020-150, Brazil., Faria JV; Toxoplasmosis and other Protozooses Laboratory, Evaluation and Promotion of the Ambiental Health Laboratory, Oswaldo Cruz Foundation, Oswaldo Cruz Institute, Rio de Janeiro, RJ, Brazil.; Postgraduate Program in Sciences and Biotechnology, Biology Institute, Universidade Federal Fluminense, RJ, Niterói, Brazil., Bello ML; Departamento de Fármacos E Medicamentos, Faculdade de Farmácia, Universidade Federal Do Rio de Janeiro, Rio de Janeiro, RJ, Brazil., Lima CGS; Departamento de Química Orgânica, Instituto de Química, Universidade Federal Fluminense, Campus do Valonguinho, Niterói, RJ, 24020-150, Brazil., Pauli FP; Departamento de Química Orgânica, Instituto de Química, Universidade Federal Fluminense, Campus do Valonguinho, Niterói, RJ, 24020-150, Brazil., Borges AA; Departamento de Química Orgânica, Instituto de Química, Universidade Federal Fluminense, Campus do Valonguinho, Niterói, RJ, 24020-150, Brazil., Rocha DR; Departamento de Química Orgânica, Instituto de Química, Universidade Federal Fluminense, Campus do Valonguinho, Niterói, RJ, 24020-150, Brazil., Moraes MG; Departamento de Química Orgânica, Instituto de Química, Universidade Federal Fluminense, Campus do Valonguinho, Niterói, RJ, 24020-150, Brazil., Forezi LSM; Departamento de Química Orgânica, Instituto de Química, Universidade Federal Fluminense, Campus do Valonguinho, Niterói, RJ, 24020-150, Brazil., Ferreira VF; Departamento de Química Orgânica, Instituto de Química, Universidade Federal Fluminense, Campus do Valonguinho, Niterói, RJ, 24020-150, Brazil., Faria RX; Toxoplasmosis and other Protozooses Laboratory, Evaluation and Promotion of the Ambiental Health Laboratory, Oswaldo Cruz Foundation, Oswaldo Cruz Institute, Rio de Janeiro, RJ, Brazil. salvador@ioc.fiocruz.br.; Postgraduate Program in Sciences and Biotechnology, Biology Institute, Universidade Federal Fluminense, RJ, Niterói, Brazil. salvador@ioc.fiocruz.br., da Silva FC; Departamento de Química Orgânica, Instituto de Química, Universidade Federal Fluminense, Campus do Valonguinho, Niterói, RJ, 24020-150, Brazil. fcsilva@id.uff.br.
Jazyk: angličtina
Zdroj: Journal of bioenergetics and biomembranes [J Bioenerg Biomembr] 2022 Dec; Vol. 54 (5-6), pp. 227-239. Date of Electronic Publication: 2022 Sep 07.
DOI: 10.1007/s10863-022-09947-2
Abstrakt: The P2X7 receptor (P2X7R) is an ion channel that promotes the passage of ions through the membrane through brief stimulation once activated by ATP, its endogenous opener. However, prolonged stimulation with ATP, which occurs in pathological processes, opens a nonselective pore in the plasma membrane, allowing the passage of large molecules and leading to cytokine release or even cell death. In this sense, the search for new inhibitors for this receptor has attracted a great deal of attention in recent years. Considering the booming of biomass upgrading reactions in recent years and the continued efforts to synthesize biologically active molecules containing the 1,2,3-triazole ring, in the present work, we aimed to investigate whether triazole-linked menadione-furan derivatives could present P2X7R inhibitory activity. The novel compounds were tested for their inhibitory activity on ATP-induced dye uptake in peritoneal macrophages. Some have shown promising results, having displayed IC 50 values lower than that of the P2X7R inhibitor BBG. Molecular docking studies also indicated that the active compounds bind to an allosteric site on P2X7R, presenting potential P2X7R inhibition.
(© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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