Synthesis of Quinoline and Dihydroquinoline Embelin Derivatives as Cardioprotective Agents

Abstract

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.

Synthesis of novel rapanone derivatives via organocatalytic reductive C-alkylation: biological evaluation of antioxidant properties, in vivo zebrafish embryo toxicity, and docking studies

“…The method also involved the use of high quantities of silver trifluoromethane sulfonate as a catalyst, which is toxic and cost-effective. Microwave high-temperature reaction conditions, multiple-step synthesis process, and low yields further contributed to the disadvantages of this method 19 (Scheme 1b).…”