Rational design of a highly selective UGT1A1 probe and its application in drug discovery

• Published in: Sensors and actuators. B, Chemical Vol. 364; p. 131826
• Main Authors: Zhai, Xin-Fang, Yi, Yang, Yu, Rong, Kuang, Yi, Shaker, Sharpkate, Su, Hui-Fei, Ye, Guo, Liu, Chen-Rui, Qiao, Xue, Liang, Lei, Ye, Min
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.08.2022
• Subjects: Fluorescent probe; Inhibitor; Licoisoflavone D; Licorice; UGT1A1; Inhibitor; Licorice; UGT1A1; Licoisoflavone D; Fluorescent probe
• ISSN: 0925-4005; 1873-3077
• DOI: 10.1016/j.snb.2022.131826

Dynamic monitoring of the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) is of great significance for the diagnosis and treatment of UGT1A1-related metabolic diseases. Herein, we designed a novel “turn-on” fluorescent probe-NHPF with excellent UGT1A1 selectivity, high sensitivity and substrate conversion rate. Furthermore, NHPF was used for real-time imaging of endogenous UGT1A1 in living cells and drug-screening of UGT1A1 inhibitors and activators from the traditional Chinese medicine licorice. Licoisoflavone D was discovered with potent UGT1A1 inhibitory activity (IC50 = 0.57 μM). [Display omitted] •Rational design of a novel “red-shift” fluorescent probe-NHPF, with excellent UGT1A1 selectivity and high sensitivity.•The probe NHPF has the highest substrate conversion rate (92%) dramatically beyond all the reported cases. This property is crucial that ensures its reliability in drug discovery from natural products.•NHPF was successfully used for the real-time imaging of endogenous UGT1A1 in living cells.•A novel UGT1A1 inhibitor-licoisoflavone D as well as an agonist-licochalcone J were screened out from glycyrrhiza by NHPF.