喹啉
化学
吡啶
苯胺
亲核细胞
戒指(化学)
心脏毒性
亲核加成
氧化应激
立体化学
组合化学
药物化学
有机化学
生物化学
催化作用
毒性
作者
Pedro Martín-Acosta,Irene Cuadrado,Laura González‐Cofrade,Roberto Pestano,Sonsoles Hortelano,Beatriz de las Heras Herrero,Ana Estévez‐Braun
标识
DOI:10.1021/acs.jnatprod.2c00924
摘要
A set of new dihydroquinoline embelin derivatives was obtained from the reaction of the natural benzoquinone embelin (1) with anilines and aromatic aldehydes in the presence of AgOTf. The synthesis of these compounds involves the formation of a Knoevenagel adduct, followed by nucleophilic addition of aniline and subsequent electrocyclic ring closure. The scope of the reaction regarding the aldehydes and anilines was determined. Quinoline derivatives were also obtained from the corresponding dihydroquinolines under oxidation with DDQ. The cardioprotective activity of the synthesized compounds was screened using a doxorubicin-induced cardiotoxicity model in H9c2 cardiomyocytes. Some structure-activity relationships were outlined, and the best activities were achieved with quinoline-embelin derivatives having a 4-nitrophenyl group attached at the pyridine ring. The obtained results indicated that embelin derivatives 4i, 6a, 6d, 6k, and 6m could have potential as cardioprotective agents, as they attenuated a DOX-induced cardiotoxicity effect acting on oxidative stress and apoptosis.
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