1617512-27-2Relevant academic research and scientific papers
2-Substituted 3-methylnaphtho[1,2-b]furan-4,5-diones as novel L-shaped ortho-quinone substrates for NAD(P)H:quinone oxidoreductase (NQO1)
Bian, Jinlei,Deng, Bang,Xu, Lili,Xu, Xiaoli,Wang, Nan,Hu, Tianhan,Yao, Zeyu,Du, Jianyao,Yang, Li,Lei, Yonghua,Li, Xiang,Sun, Haopeng,Zhang, Xiaojin,You, Qidong
, p. 56 - 67 (2014/06/10)
A series of L-shaped ortho-quinone analogs were designed by analyzing the binding mode with NQO1. Metabolic studies demonstrated that compounds 2m, 2n and 2q exhibited higher metabolic rates than β-lapachone. The docking studies, which supported the rationalization of the metabolic studies, constituted a prospective rational basis for the development of optimized ortho-quinone analogs. Besides, good substrates (2m, 2n and 2r) for NQO1 showed higher selective toxicity than β-lapachone toward A549 (NQO1-rich) cancer cells versus H596 (NQO1-deficient) cells. Determination of superoxide (O 2?-) production and in vitro cytotoxicity evaluation in the presence of the NQO1 inhibitor dicoumarol confirmed that the ortho-quinones exerted their antitumor activity through NQO1-mediated ROS production by redox cycling. It was suggested that the L-shaped quinone substrates for NQO1 possessed better specificity and safety than β-lapachone.
