Affinity-based small fluorescent probe for NAD(P)H:quinone oxidoreductase 1 (NQO1). Design, synthesis and pharmacological evaluation.
NQO1 is a dimeric flavoprotein which intimately associated with cancer and overexpressed in the cytosol of numerous human tumor cells. Given that the cellular environment is quite dynamic and versatile, further investigation of the function of NQO1 depends on tools for specific detection of it. Currently, several activity-based assays have been developed to detect NQO1-expressing cancerous tissues. Herein, we report the development of a functional affinity-based small-molecule probe which is composed of a potent small-molecule NQO1 inhibitor 3d as the recognition group, a linker and the fluorophores group FITC. The probe exhibits good inhibitory activity of NQO1 and has been successfully used to label the protein in A549 cells at the micromolar level. These features make the probe favorable for mechanistic studies and cancer diagnostic biomarker. Based on these preliminary results, our laboratory will focus on the further development of fluorescent probe for NQO1, which could be anticipated to be applied in physiological and pathological studies of NQO1.
State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 210009, China.
Jinlei
J
Bian
State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 210009, China.
Xiang
X
Li
State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 210009, China.
Lili
L
Xu
State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 210009, China.
Nan
N
Wang
State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 210009, China.
Xue
X
Qian
State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 210009, China. Electronic address: youqd@163.com.
Qidong
Q
You
State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 210009, China; Department of Organic Chemistry, China Pharmaceutical University, Nanjing, 210009, China. Electronic address: zxj@cpu.edu.cn.
Xiaojin
X
Zhang
D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D062105:Molecular Docking Simulation; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D061848:Optical Imaging; D011487:Protein Conformation; D013379:Substrate Specificity
D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human
Dicoumarol; FITC; Fluorescent probe; Inhibitor; NQO1