Antioxidant and neuroprotective activities of selected 2-pyridones: In vitro and in silico study

• Published in: Journal of molecular structure Vol. 1256; p. 132546
• Main Authors: Lunić, Tanja, Lađarević, Jelena, Mandić, Marija, Veruševski, Vanja, Nedeljković, Biljana Božić, Mijin, Dušan, Božić, Bojan
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 15.05.2022
• Subjects: Antioxidants; Docking study; Neuroinflammation; Neuroprotection; Pyridone derivatives; Antioxidants; Neuroprotection; Neuroinflammation; Pyridone derivatives; Docking study
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2022.132546

•Seven selected 2-pyridones exhibited excellent antioxidant activities.•Significant anti-neuroinflammatory activity was observed in vitro using BV2 cells.•Significant neuroprotective activity was detected in vitro using SH-SY5Y cells.•Docking study revealed interactions with iNOS and TLR4 signaling pathway proteins. Series of twenty-four 2-pyridone derivatives were screened and selected using the antioxidant ABTS assay in order to find the most prominent compounds for further in vitro and in silico analyses. Seven derivatives with the highest antioxidant activities were selected and evaluated by β-carotene bleaching assay, where all of the compounds exhibited better activities than standard antioxidant substance, vitamin C. Furthermore, seven selected 2-pyridones exhibited significant anti-neuroinflammatory activity by reducing the production of pro-inflammatory mediators (ROS, NO, IL-6, and TNF-α) by LPS-stimulated BV2 microglial cells. Moreover, neuroprotective activity in microglia supernatant transfer model system on SH-SY5Y neuronal cells has been observed. Anti-neuroinflammatory mechanisms of selected 2-pyridones have been investigated by molecular docking studies of the TLR4 signaling pathway proteins as well as inducible nitric oxide synthase. The present study suggests that selected 2-pyridone derivatives can alleviate neuroinflammation in microglial cells and protect the surrounding neuronal cells from damage, which qualifies them for further investigations towards neurodegenerative diseases associated with inflammation. [Display omitted]