Department of Chemistry and Institute of Applied Chemistry, Hallym University, Chuncheon 24252, Korea.
Department of Life Science and Multidisciplinary Genome Institute, Hallym University, Chuncheon 24252, Korea.
Molecules. 2021 Jan 26;26(3):646. doi: 10.3390/molecules26030646.
The research on resveratrol () has been conducted intensively over a long time due to its proven antioxidant activity and disease-fighting capabilities. Many efforts have also been made to increase these biological effects. In the present study, six new extended aromatic resveratrol analogues containing naphthalene () and its bioisosteres quinoline ( and ), isoquinoline () quinoxaline () and quinazoline () scaffolds were designed and synthesized using an annulation strategy. The antioxidant and anti-inflammatory activities of these compounds were investigated. All compounds showed better antioxidant activity than resveratrol in ABTS assay. As for the anti-inflammatory test, and exhibited better activity than resveratrol. It is worth noting that nitrogen substitution on the extended aromatic resveratrol analogues has a significant impact on cell viability. Taking the antioxidant activities and NO inhibition activities into consideration, we conclude that isoquinoline analogue may qualify for the further investigation of antioxidant and anti-inflammatory therapy. Furthermore, our study results suggest that in order to improve the biological activity of polyphenolic compounds, extended aromaticity and nitrogen substitution strategy could be a viable method for the design of future drug candidates.
由于白藜芦醇（resveratrol）已被证实具有抗氧化活性和抵抗疾病的能力，因此其相关研究已经持续了很长一段时间。人们还做出了许多努力来提高这些生物效应。在本研究中，设计并合成了 6 种新的含有萘（naphthalene）及其生物等排体喹啉（quinoline）、异喹啉（isoquinoline）、喹喔啉（quinoxaline）和喹唑啉（quinazoline）支架的扩展芳香族白藜芦醇类似物，采用了环合策略。研究了这些化合物的抗氧化和抗炎活性。在 ABTS 测定中，所有化合物均显示出比白藜芦醇更好的抗氧化活性。至于抗炎测试，和比白藜芦醇具有更好的活性。值得注意的是，扩展芳香族白藜芦醇类似物上的氮取代对细胞活力有重大影响。考虑到抗氧化活性和 NO 抑制活性，我们得出结论，异喹啉类似物 可能有资格进一步研究抗氧化和抗炎治疗。此外，我们的研究结果表明，为了提高多酚类化合物的生物活性，扩展芳香性和氮取代策略可能是设计未来药物候选物的可行方法。
