Discovery of MAGL Inhibition by Lophine Derivatives: An Unexpected Finding from Chemiluminescent Assay Development DOI Creative Commons
Roberta Ottria, Silvana Casati, Ornella Xynomilakis

и другие.

Molecules, Год журнала: 2025, Номер 30(7), С. 1605 - 1605

Опубликована: Апрель 3, 2025

The inhibitory effects of two novel lophine derivatives were unexpectedly discovered during the development a chemiluminescent monoacylglycerol lipase (MAGL) assay. proposed found to exhibit concentration-dependent on MAGL with octanoic and palmitic acid esters 2-(4-hydroxyphenyl)-4,5-diphenylimidazole showing strongest activity. Reversibility assays using fluorometric method confirmed that these compounds interact in stable, irreversible manner. To further investigate their mode interaction, docking studies performed, supporting hypothesis 3 4 may act as competitive inhibitors. Lophine initially designed synthesized potential chemiluminescence pro-enhancers. However, assay optimization revealed no signal production upon hydrolysis, precluding use probes. These findings suggest is promising candidate for inhibitors, although needed enhance binding affinity selectivity.

Язык: Английский

Discovery of MAGL Inhibition by Lophine Derivatives: An Unexpected Finding from Chemiluminescent Assay Development DOI Creative Commons
Roberta Ottria, Silvana Casati, Ornella Xynomilakis

и другие.

Molecules, Год журнала: 2025, Номер 30(7), С. 1605 - 1605

Опубликована: Апрель 3, 2025

The inhibitory effects of two novel lophine derivatives were unexpectedly discovered during the development a chemiluminescent monoacylglycerol lipase (MAGL) assay. proposed found to exhibit concentration-dependent on MAGL with octanoic and palmitic acid esters 2-(4-hydroxyphenyl)-4,5-diphenylimidazole showing strongest activity. Reversibility assays using fluorometric method confirmed that these compounds interact in stable, irreversible manner. To further investigate their mode interaction, docking studies performed, supporting hypothesis 3 4 may act as competitive inhibitors. Lophine initially designed synthesized potential chemiluminescence pro-enhancers. However, assay optimization revealed no signal production upon hydrolysis, precluding use probes. These findings suggest is promising candidate for inhibitors, although needed enhance binding affinity selectivity.

Язык: Английский

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