Synthesis and 5-lipoxygenase inhibitory activity of new cinnamoyl and caffeoylclusters

Doiron, Jérémie A.; Boudreau, Luc H.; Picot, Nadia; Villebonet, Benoît; Surette, Marc E.; Touaibia, Mohamed

doi:10.1016/j.bmcl.2008.12.108

Cited by 28 publications

(30 citation statements)

References 26 publications

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“…1) such as caffeic acid is well known [21]–[23]. This would explain the results obtained with octyl methoxycinnamate and isoamyl p-methoxycinnamate.…”

Section: Resultsmentioning

confidence: 78%

UV Filters, Ingredients with a Recognized Anti-Inflammatory Effect

et al. 2012

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BackgroundTo explain observed differences during SPF determination using either an in vivo or in vitro method, we hypothesized on the presence of ingredients having anti-inflammatory properties.Methodology/Principal FindingsTo research our hypothesis, we studied the 21 UV filters both available on the market and authorized by European regulations and subjected these filters to the phorbol-myristate-acetate test using mice. We then catalogued the 13 filters demonstrating a significant anti-inflammatory effect with edema inhibition percentages of more than 70%. The filters are: diethylhexyl butamido triazone (92%), benzophenone-5 and titanium dioxide (90%), benzophenone-3 (83%), octocrylène and isoamyl p-methoxycinnamate (82%), PEG-25 PABA and homosalate (80%), octyl triazone and phenylbenzimidazole sulfonic acid (78%), octyl dimethyl PABA (75%), bis-ethylhexyloxyphenol methoxyphenyl triazine and diethylamino hydroxybenzoyl hexylbenzoate (70%). These filters were tested at various concentrations, including their maximum authorized dose. We detected a dose-response relationship.Conclusions/SignificanceThe anti-inflammatory effect of a sunscreen ingredient may affect the in vivo SPF value.

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“…1) such as caffeic acid is well known [21]–[23]. This would explain the results obtained with octyl methoxycinnamate and isoamyl p-methoxycinnamate.…”

Section: Resultsmentioning

confidence: 78%

UV Filters, Ingredients with a Recognized Anti-Inflammatory Effect

et al. 2012

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“…HEK293 cells stably transfected with 5‐LO and 5‐LO‐activating protein (FLAP) were used to screen compounds for 5‐LO inhibition as previously described. As shown in Figure , para ‐, meta ‐, and ortho ‐coumaric acid phenethylesters ( 4 , 5, 6 ) had no inhibitory activity as opposed to zileuton ( 1 ) and CAPE ( 2 ), which highlights the importance of multiple oxygenated positions on this aromatic ring (Figure ).…”

Section: Resultsmentioning

confidence: 99%

“…Cells were then stimulated for 15 min at 37°C with the addition of 10 μ m calcium ionophore A23187 (Sigma‐Aldrich, Oakville, ON, Canada) and 10 μ m arachidonic acid (Cayman Chemical, Ann Arbor, MI). Stimulations were stopped and processed for RP‐HPLC analysis as described previously . Data are expressed as mean ± Standard Error of the Mean (SEM) of three independent experiments, each performed in duplicate (Figures and ).…”

Section: Methodsmentioning

confidence: 99%

Sinapic acid phenethyl ester as a potent selective 5‐lipoxygenase inhibitor: Synthesis and structure–activity relationship

et al. 2018

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Given the hepatotoxicity and an unfavorable pharmacokinetic profile of zileuton (Zyflo ), currently the only approved and clinically used 5-Lipoxygenase (5-LO) inhibitor, the search for potent and safe 5-LO inhibitors is highly demanded. The action of several phenolic acid phenethyl esters as potential 5-Lipoxygenase (5-LO) inhibitors has been investigated. For this purpose, a series of 14 phenethyl esters was synthesized and their impact on 5-LO inhibition was evaluated. The effects of position and number of hydroxyl and methoxy groups on the phenolic acid were investigated. The shortening of the linker between the carbonyl and the catechol moiety as well as the presence of the α,β-unsaturated carbonyl group was also explored. The sinapic acid phenethyl ester (10), which can be named SAPE (10) by analogy to caffeic acid phenethyl ester (CAPE), inhibited 5-LO in a concentration-dependent manner and outperformed both zileuton (1) and CAPE (2). With an IC of 0.3 μm, SAPE (10) was threefold more potent than CAPE (2) and 10-fold more potent than zileuton (1), the only 5-LO inhibitor approved for clinical use. Unlike CAPE (2), SAPE (10) had no effect on 12-lipoxygenase (12-LO) and less effect on cyclooxygenase 1 (COX-1) which makes it a more selective 5-LO inhibitor.

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“…Amongst these are polyhydroxylated products such as caffeic acid and related compounds that are widely distributed in plants and exhibit anti-oxidant [11]–[13] and anti-inflammatory properties [14], [15]. Synthetic caffeic acid analogues were recently shown to be promising 5-LO inhibitors [14], [16], [17], while caffeic acid and its naturally-occurring analogue, caffeic acid phenethyl ester (CAPE, Figure 1), a component of propolis from honeybee hives, were reported to inhibit LT production in mouse peritoneal macrophages [14].…”

Section: Introductionmentioning

confidence: 99%

Caffeic Acid Phenethyl Ester and Its Amide Analogue Are Potent Inhibitors of Leukotriene Biosynthesis in Human Polymorphonuclear Leukocytes

et al. 2012

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Background5-lipoxygenase (5-LO) catalyses the transformation of arachidonic acid (AA) into leukotrienes (LTs), which are important lipid mediators of inflammation. LTs have been directly implicated in inflammatory diseases like asthma, atherosclerosis and rheumatoid arthritis; therefore inhibition of LT biosynthesis is a strategy for the treatment of these chronic diseases.Methodology/Principal FindingsAnalogues of caffeic acid, including the naturally-occurring caffeic acid phenethyl ester (CAPE), were synthesized and evaluated for their capacity to inhibit 5-LO and LTs biosynthesis in human polymorphonuclear leukocytes (PMNL) and whole blood. Anti-free radical and anti-oxidant activities of the compounds were also measured. Caffeic acid did not inhibit 5-LO activity or LT biosynthesis at concentrations up to 10 µM. CAPE inhibited 5-LO activity (IC50 0.13 µM, 95% CI 0.08–0.23 µM) more effectively than the clinically-approved 5-LO inhibitor zileuton (IC50 3.5 µM, 95% CI 2.3–5.4 µM). CAPE was also more effective than zileuton for the inhibition of LT biosynthesis in PMNL but the compounds were equipotent in whole blood. The activity of the amide analogue of CAPE was similar to that of zileuton. Inhibition of LT biosynthesis by CAPE was the result of the inhibition of 5-LO and of AA release. Caffeic acid, CAPE and its amide analog were free radical scavengers and antioxidants with IC50 values in the low µM range; however, the phenethyl moiety of CAPE was required for effective inhibition of 5-LO and LT biosynthesis.ConclusionsCAPE is a potent LT biosynthesis inhibitor that blocks 5-LO activity and AA release. The CAPE structure can be used as a framework for the rational design of stable and potent inhibitors of LT biosynthesis.

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Synthesis and 5-lipoxygenase inhibitory activity of new cinnamoyl and caffeoylclusters

Cited by 28 publications

References 26 publications

UV Filters, Ingredients with a Recognized Anti-Inflammatory Effect

UV Filters, Ingredients with a Recognized Anti-Inflammatory Effect

Sinapic acid phenethyl ester as a potent selective 5‐lipoxygenase inhibitor: Synthesis and structure–activity relationship

Caffeic Acid Phenethyl Ester and Its Amide Analogue Are Potent Inhibitors of Leukotriene Biosynthesis in Human Polymorphonuclear Leukocytes

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