Antioxidant and anti-inflammatory properties of 1,2,4-oxadiazole analogs of resveratrol.
The chemopreventive properties of resveratrol are ascribed mostly to its antioxidant activity, in particular its scavenging ability for reactive oxygen species (ROS), and to the inhibition of NF-κB pathway which has also been suggested as an important underlying mechanism of its reported properties. In present study, a small library of nine 1,2,4-oxadiazole-based structural analogs of resveratrol were assayed for their antioxidant and anti-inflammatory activities. Several compounds showed significant inhibitory activities against NF-κB and/or ROS production. Compound 2, incorporating two para-hydroxyphenyl moieties connected by the 1,2,4-oxadiazole ring, was the most active, its potency in inhibiting activation of NF-κB and ROS scavenging abilities surpassing that of resveratrol. Additionally, we elucidated the mechanisms underlying the NF-κB inhibitory activity of compound 2. Finally, in contrast to resveratrol, compound 2 significantly reduced the LPS-induced release of pro-inflammatory cytokines, indicating its prominent anti-inflammatory potential.
Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, SI-1000 Ljubljana, Slovenia.
Martina
M
Gobec
Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, SI-1000 Ljubljana, Slovenia.
Tihomir
T
Tomašič
Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, SI-1000 Ljubljana, Slovenia.
Tijana
T
Markovič
Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, SI-1000 Ljubljana, Slovenia.
Irena
I
Mlinarič-Raščan
Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, SI-1000 Ljubljana, Slovenia.
Marija Sollner
MS
Dolenc
Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, SI-1000 Ljubljana, Slovenia. Electronic address: ziga.jakopin@ffa.uni-lj.si.
Žiga
Ž
Jakopin
D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D008958:Models, Molecular; D010069:Oxadiazoles / Q000737:chemistry / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*; D000097782:NF-kappaB-Inducing Kinase
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D010069:Oxadiazoles; D017346:Protein Serine-Threonine Kinases; D017382:Reactive Oxygen Species; D000077185:Resveratrol; D013267:Stilbenes; D000097782:NF-kappaB-Inducing Kinase
1,2,4-Oxadiazole; Anti-Inflammatory; Antioxidant; NF-κB inhibition; Resveratrol