Anti-Inflammatory Activity of Soluble Epoxide Hydrolase Inhibitors Based on Selenoureas Bearing an Adamantane Moiety

Burmistrov, V. V.; Morisseau, Christophe; Babkov, Denis A.; Голубева, Т. С.; Pitushkin, D. A.; Sokolova, Elena; Vasipov, V.V.; Kuznetsov, Ya. P.; Bazhenov, Sergey V.; Novoyatlova, Uliana S.; Bondarev, Nikolay A.; Манухов, И. В.; Осипова, В. П.; Берберова, Н. Т.; Spasov, A. A.; Бутов, Г. М.; Hammock, Bruce D.

doi:10.3390/ijms231810710

Cited by 7 publications

(3 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Frontiers in Chemistry frontiersin.org 06 has shown significant potential in recent years. Some adamantane-type compounds have demonstrated promising biological activities, such as anti-psychiatric, anticancer and neurological disorders, and anti-inflammatory effects (Burmistrov et al, 2022;Tao et al, 2024;Gutti et al, 2023;Ragshaniya et al, 2024). To explore this further, we have utilized the uniqueness of the adamantane moiety in our synthetic compounds with the introduction of various functional groups that may enhance the potency as well as selectivity.…”

Section: Resultsmentioning

confidence: 99%

Asymmetric aza-Henry reaction toward trifluoromethyl β-nitroamines and biological investigation of their adamantane-type derivatives

Ren,

Du,

Peng

et al. 2024

Front. Chem.

View full text Add to dashboard Cite

Amino acid-derived quaternary ammonium salts were successfully applied in the asymmetric aza-Henry reaction of nitromethane to N-Boc trifluoromethyl ketimines. α-Trifluoromethyl β-nitroamines were synthesized in good to excellent yields with moderate to good enantioselectivities. This reaction is distinguished by its mild conditions, low catalyst loading (1 mol%), and catalytic base. It also proceeded on a gram scale without loss of enantioselectivity. The products were transformed to a series of adamantane-type compounds containing chiral trifluoromethylamine fragments. The potent anticancer activities of these compounds against liver cancer HepG2 and melanoma B16F10 were evaluated. Six promising compounds with notable efficacy have potential for further development.

show abstract

Section: Resultsmentioning

confidence: 99%

Asymmetric aza-Henry reaction toward trifluoromethyl β-nitroamines and biological investigation of their adamantane-type derivatives

Ren,

Du,

Peng

et al. 2024

Front. Chem.

View full text Add to dashboard Cite

show abstract

“…We also tested whether our activators modulated sEH activity. While sEH does not lie in the biochemical pathway for NAE biosynthesis or metabolism, inhibition or genetic ablation of sEH increases the levels of epoxy fatty acids and, thereby, exerts biological effects similar to the known effects of NAEs such as reducing obesity, cardiovascular disease, pain, and inflammation. – Graded concentrations of VU534 showed modest inhibition of sEH (IC 50 = 1.2 μM, 95% CI = 0.5–2.4 μM, maximal inhibition = 55%), while neither VU533 nor VU233 significantly inhibited sEH (Figure B). Other compounds of our series showed variable effects on FAAH and sEH activity (Figures S7 and S8).…”

Section: Resultsmentioning

confidence: 99%

Small Molecule Activation of NAPE-PLD Enhances Efferocytosis by Macrophages

et al. 2023

View full text Add to dashboard Cite

“…We also tested whether our activators modulated sEH activity. While sEH does not lie in the biochemical pathway for NAE biosynthesis or metabolism, inhibition or genetic ablation of sEH increases the levels of epoxy fatty acids 20 and thereby exerts biological effects similar to the known effects of NAEs such as reducing obesity, cardiovascular disease, pain, and inflammation [20][21][22][23] . Graded concentrations of VU534 showed modest inhibition of sEH (IC 50 1.2 µM, 95% CI 0.5-2.4 µM, maximal inhibition 55%), while neither VU533 nor VU233 significantly inhibited seH (Figure 6B).…”

Section: Biochemical Characterization Of Lead Nape-pld Activatorsmentioning

confidence: 99%

Small Molecule Activation of NAPE-PLD Enhances Efferocytosis by Macrophages

Zarrow

Alli-Oluwafuyi

Youwakim

et al. 2023

Preprint

View full text Add to dashboard Cite

N-acyl-phosphatidylethanolamine hydrolyzing phospholipase D (NAPE-PLD) is a zinc metallohydrolase that hydrolyzesN-acyl-phosphatidylethanolamine (NAPEs) to formN-acyl-ethanolamides (NAEs) and phosphatidic acid. Several lines of evidence suggest that reduced NAPE-PLD activity could contribute to cardiometabolic diseases. For instance,NAPEPLDexpression is reduced in human coronary arteries with unstable atherosclerotic lesions, defective efferocytosis is implicated in the enlargement of necrotic cores of these lesions, and NAPE-PLD products such as palmitoylethanolamide and oleoylethanolamide have been shown to enhance efferocytosis. Thus, enzyme activation mediated by a small molecule may serve as a therapeutic treatment for cardiometabolic diseases. As a proof-of-concept study, we sought to identify small molecule activators of NAPE-PLD. High-throughput screening followed by hit validation and primary lead optimization studies identified a series of benzothiazole phenylsulfonyl-piperidine carboxamides that variably increased activity of both mouse and human NAPE-PLD. From this set of small molecules, two NAPE-PLD activators (VU534 and VU533) were shown to increase efferocytosis by bone-marrow derived macrophages isolated from wild-type mice, while efferocytosis was significantly reduced inNapepld-/-BMDM or after Nape-pld inhibition. Together these studies demonstrate an essential role for NAPE-PLD in the regulation of efferocytosis and the potential value of NAPE-PLD activators as a strategy to treat cardiometabolic diseases.

show abstract

Anti-Inflammatory Activity of Soluble Epoxide Hydrolase Inhibitors Based on Selenoureas Bearing an Adamantane Moiety

Abstract: This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

Cited by 7 publications

References 48 publications

Asymmetric aza-Henry reaction toward trifluoromethyl β-nitroamines and biological investigation of their adamantane-type derivatives

Asymmetric aza-Henry reaction toward trifluoromethyl β-nitroamines and biological investigation of their adamantane-type derivatives

Small Molecule Activation of NAPE-PLD Enhances Efferocytosis by Macrophages

Small Molecule Activation of NAPE-PLD Enhances Efferocytosis by Macrophages

Contact Info

Product

Resources

About