Design, synthesis, and biological evaluation of 4-substituted-3,4-dihydrobenzo[h]quinoline-2,5,6(1H)-triones as NQO1-directed antitumor agents.

Li-Qiang Wu, Xin Ma, Chong Zhang, Zhao-Peng Liu

European journal of medicinal chemistry 2020 Jul 15

filter terms:

A novel series of 4-substituted-3,4-dihydrobenzo[h]quinoline-2,5,6(1H)-triones as NQO1-directed antitumor agents were designed, synthesized, biologically evaluated. Compounds 3n, 3o and 3j proved to be good NQO1 substrates that showed increased metabolic rates relative to that of β-lapachone. In addition, 3n, 3o and 3j potently inhibited the growth of NQO1-rich breast cancer MCF-7 cell, liver hepatocellular HepG2 cell, and lung cancer A549 cell. In cellular mechanistic studies, the representative compound 3o triggered ROS generation depending on the NQO1 dose, and induce HepG2 cell apoptosis by the generated oxidative stress. In HepG2 xenografts mouse model, at the dose of 20 mg/kg, 3o remarkably suppressed the tumor growth without affecting the animal weights. Copyright © 2020 Elsevier Masson SAS. All rights reserved.

Citation

Li-Qiang Wu, Xin Ma, Chong Zhang, Zhao-Peng Liu. Design, synthesis, and biological evaluation of 4-substituted-3,4-dihydrobenzo[h]quinoline-2,5,6(1H)-triones as NQO1-directed antitumor agents. European journal of medicinal chemistry. 2020 Jul 15;198:112396