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

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 IC50 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.

Menadione: a platform and a target to valuable compounds synthesis.

Naphthoquinones are important natural or synthetic compounds belonging to the general class of quinones. Many compounds in this class have become drugs that are on the pharmaceutical market for the treatment of various diseases. A special naphthoquinone derivative is menadione, a synthetic naphthoquinone belonging to the vitamin K group. This compound can be synthesized by different methods and it has a broad range of biological and synthetic applications, which will be highlighted in this review.

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis.

Several low molecular weight naphthoquinones are very useful in organic synthesis. These compounds have given rise to thousands of other naphthoquinones that have been tested against various microorganisms and pharmacological targets, including being used in the preparation of several drugs that are on the pharmaceutical market. Among these naphthoquinones, the series of compounds prepared from 1,2-naphthoquinone-4-sulfonic acid salts (ß-NQS) stands out. In addition to being used in organic synthesis, they are excellent analytical derivatization reagents to spectrophotometrically determine drugs containing primary and secondary amino groups. This review summarizes the literature involving ß-NQS.