Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.
Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Chem Biol Drug Des. 2018 Jun;91(6):1125-1132. doi: 10.1111/cbdd.13174. Epub 2018 Feb 26.
Inflammations, sensitivities, and some cancers in mammals are intimately linked to the activity of lipo-oxygenase enzymes. Owing to the importance of these enzymes, mechanistic studies, product analysis, and synthesis of inhibitors have expanded. In this study, a series of hydroxycoumarins, methoxy-3-hydroxy coumarins, and 7-alkoxy-3-hydroxy coumarins were synthesized and evaluated as potential inhibitors of human 15-LOX-1. Among the synthetic coumarins, 7-methoxy-3-hydroxycoumarin derivative demonstrated potent inhibitory activity and the compound, 5f, showed the best result. Radical scavenging assessment, IC , HNMR, and DPPH bleaching results indicate that the electronic properties are the major factors for the lipo-oxygenase inhibition potency of the synthetic coumarins. Based on the theoretical studies, it was suggested that the mesomeric effect of the substituent at the seventh position of the benzene ring is one of the major factors in the stability of the oxy-radical intermediate.
在哺乳动物中，炎症、过敏和某些癌症与脂氧合酶的活性密切相关。由于这些酶的重要性，对其的机制研究、产物分析和抑制剂的合成都得到了扩展。在这项研究中，我们合成了一系列羟基香豆素、甲氧基-3-羟基香豆素和 7-烷氧基-3-羟基香豆素，并将其评估为潜在的人 15-脂氧合酶-1 抑制剂。在所合成的香豆素中，7-甲氧基-3-羟基香豆素衍生物表现出很强的抑制活性，化合物 5f 表现出最好的结果。自由基清除评估、IC 、HNMR 和 DPPH 褪色结果表明，电子性质是合成香豆素抑制脂氧合酶活性的主要因素。基于理论研究，我们认为苯环第七位取代基的中介效应是氧自由基中间物稳定性的主要因素之一。
