Bibliographic Details
| Title: |
Discovery of MAGL Inhibition by Lophine Derivatives: An Unexpected Finding from Chemiluminescent Assay Development. |
| Authors: |
Ottria, Roberta1 (AUTHOR) roberta.ottria@unimi.it, Casati, Silvana1,2 (AUTHOR), Xynomilakis, Ornella1 (AUTHOR), Veselinović, Aleksandar2 (AUTHOR), Ciuffreda, Pierangela1 (AUTHOR) |
| Source: |
Molecules. Apr2025, Vol. 30 Issue 7, p1605. 18p. |
| Subject Terms: |
*CHEMILUMINESCENCE assay, *OCTANOIC acid, *MOLECULAR docking, *PALMITIC acid, *LIPASES |
| Abstract: |
The inhibitory effects of two novel lophine derivatives were unexpectedly discovered during the development of a chemiluminescent monoacylglycerol lipase (MAGL) assay. The proposed lophine derivatives were found to exhibit concentration-dependent inhibitory effects on MAGL with the octanoic and palmitic acid esters of 2-(4-hydroxyphenyl)-4,5-diphenylimidazole showing the strongest activity. Reversibility assays using a fluorometric method confirmed that these compounds interact with MAGL in a stable, irreversible manner. To further investigate their mode of interaction, docking studies were performed, supporting the hypothesis that compounds 3 and 4 may act as competitive and irreversible inhibitors. Lophine derivatives were initially designed and synthesized as potential chemiluminescence pro-enhancers. However, assay optimization revealed no signal production upon MAGL hydrolysis, precluding their use as chemiluminescent probes. These findings suggest that lophine is a promising candidate for the development of MAGL inhibitors, although further optimization is needed to enhance binding affinity and selectivity. [ABSTRACT FROM AUTHOR] |
|
Copyright of Molecules is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| Database: |
Academic Search Complete |
|
Full text is not displayed to guests. |
Login for full access.
|
