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Start Over Author "Li, Yaoguang" Publisher elsevier bv
20 results on '"Li, Yaoguang"'

10. Design, synthesis, and structure-activity relationship study of glycyrrhetinic acid derivatives as potent and selective inhibitors against human carboxylesterase 2

Author

Li Yaoguang, Jie Hou, Ling Yang, Li-Wei Zou, Da-Cheng Hao, Ping Wang, Kun Zhou, Qiang Jin, and Guang-Bo Ge

Subjects
0301 basic medicine, Stereochemistry, 01 natural sciences, Carboxylesterase, Structure-Activity Relationship, 03 medical and health sciences, Drug Discovery, Humans, Structure–activity relationship, Moiety, Enzyme Inhibitors, IC50, Pharmacology, biology, 010405 organic chemistry, Chemistry, Organic Chemistry, Active site, General Medicine, Prodrug, 0104 chemical sciences, Bioavailability, Molecular Docking Simulation, 030104 developmental biology, Drug Design, biology.protein, Glycyrrhetinic Acid, Selectivity
Abstract

Human carboxylesterase 2 (hCE2), one of the major carboxylesterases in the human intestine and various tumour tissues, plays important roles in the oral bioavailability and treatment outcomes of ester- or amide-containing drugs or prodrugs, such as anticancer agents CPT-11 (irinotecan) and LY2334737 (gemcitabine). In this study, 18β-glycyrrhetinic acid (GA), the most abundant pentacyclic triterpenoid from natural source, was selected as a reference compound for the development of potent and specific inhibitors against hCE2. Simple semi-synthetic modulation on GA was performed to obtain a series of GA derivatives. Structure-activity relationship analysis brought novel insights into the structure modification of GA. Converting the 11-oxo-12-ene of GA to 12-diene moiety, and C-3 hydroxyl and C-30 carboxyl group to 3-O-β-carboxypropionyl and ethyl ester respectively, led to a significant enhancement of the inhibitory effect on hCE2 and the selectivity over hCE1. These exciting findings inspired us to design and synthesize the more potent compound 15 (IC50 0.02 μM) as a novel and highly selective inhibitor against hCE2, which was 3463-fold more potent than the parent compound GA and demonstrated excellent selectivity (>1000-fold over hCE1). The molecular docking study of compound 15 and the active site of hCE1 and hCE2 demonstrated that the potent and selective inhibition of compound 15 toward hCE2 could partially be attributed to its relatively stronger interactions with hCE2 than with hCE1.

Published
2016

15. Fructus Psoraleae contains natural compounds with potent inhibitory effects towards human carboxylesterase 2

Author

Ping Wang, Jia-Yan Ren, Ling Yang, Li Yaoguang, Liu Zhaoming, Jie Hou, Xia Lv, Jing Ning, Shi-Yang Li, and Guang-Bo Ge

Subjects
Flavonoids, Pharmacology, Chemistry, General Medicine, Flavones, Inhibitory postsynaptic potential, Fructus psoraleae, Isoflavones, Carboxylesterase, Psoralea, chemistry.chemical_compound, Chalcones, Phenols, Fruit, Activity profiling, Drug Discovery, Neobavaisoflavone, Humans, Enzyme Inhibitors, Bavachinin, Drugs, Chinese Herbal, Bakuchiol
Abstract

Fructus Psoraleae (FP) is an edible Chinese herbal which is widely used in Asia for the treatment of various diseases including asthma, diarrhea, and osteoporosis. This study aimed to investigate the inhibitory effects of the crude ethanol extract from FP on human carboxylesterase 2 (hCE2), as well as to identity and characterize the naturally occurring inhibitors of hCE2 in FP. Our results demonstrated that the ethanol extract of FP displayed potent inhibitory effects towards hCE2, while five major bioactive constitutes in FP were efficiently identified by LC-DAD-ESI-MS/MS, with the aid of LC-based activity profiling. The identified bioactive compounds including neobavaisoflavone, isobavachalcone, bavachinin, corylifol A and bakuchiol were found to be naturally occurring potent inhibitors of hCE2, with low Ki values ranging from 0.62μM to 3.89μM. This is the first report of the chemical constitutes in FP as potent inhibitors of hCE2.

Published
2015

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