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Your search keyword '"Chen, Yeh-Long"' showing total 8 results
Start Over Author "Chen, Yeh-Long" Journal journal of medicinal chemistry
8 results on '"Chen, Yeh-Long"'

1. Discovery of an Orally Efficacious MYC Inhibitor for Liver Cancer Using a GNMT-Based High-Throughput Screening System and Structure–Activity Relationship Analysis

Author

Kant, Rajni, primary, Yang, Ming-Hui, additional, Tseng, Chih-Hua, additional, Yen, Chia-Hung, additional, Li, Wei-You, additional, Tyan, Yu-Chang, additional, Chen, Marcelo, additional, Tzeng, Cherng-Chyi, additional, Chen, Wei-Cheng, additional, You, Kaiting, additional, Wang, Wen-Chieh, additional, Chen, Yeh-Long, additional, and Chen, Yi-Ming Arthur, additional

Published
2021
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8. Specific Inhibition of Bacterial β-Glucuronidase by Pyrazolo[4,3-c]quinoline Derivatives via a pH-Dependent Manner To Suppress Chemotherapy-Induced Intestinal Toxicity.

Author

Cheng KW, Tseng CH, Yang CN, Tzeng CC, Cheng TC, Leu YL, Chuang YC, Wang JY, Lu YC, Chen YL, and Cheng TL

Subjects
Animals, Antineoplastic Agents adverse effects, Camptothecin adverse effects, Camptothecin analogs & derivatives, Diarrhea prevention & control, Drug Screening Assays, Antitumor, Escherichia coli, Glucuronidase chemistry, High-Throughput Screening Assays, Humans, Hydrogen-Ion Concentration, Intestines pathology, Irinotecan, Mice, Molecular Docking Simulation, Protective Agents administration & dosage, Protective Agents chemical synthesis, Pyrazoles administration & dosage, Pyrazoles chemical synthesis, Quinolines administration & dosage, Quinolines chemical synthesis, Structure-Activity Relationship, Glucuronidase antagonists & inhibitors, Intestines drug effects, Protective Agents pharmacology, Pyrazoles pharmacology, Quinolines pharmacology
Abstract

The direct inhibition of bacterial β-glucuronidase (βG) activity is expected to reduce the reactivation of glucuronide-conjugated drugs in the intestine, thereby reducing drug toxicity. In this study, we report on the effects of pyrazolo[4,3-c]quinolines acting as a new class of bacterial βG-specific inhibitors in a pH-dependent manner. Refinement of this chemotype for establishing structure-activity relationship resulted in the identification of potential leads. Notably, the oral administration of 3-amino-4-(4-fluorophenylamino)-1H-pyrazolo[4,3-c]quinoline (42) combined with chemotherapeutic CPT-11 treatment prevented CPT-11-induced serious diarrhea while maintaining the antitumor efficacy in tumor-bearing mice. Importantly, the inhibitory effects of 42 to E. coli βG was reduced as the pH decreased due to the various surface charges of the active pocket of the enzyme, which may make their combination more favorable at neutral pH. These results demonstrate novel insights into the potent bacterial βG-specific inhibitor that would allow this inhibitor to be used for the purpose of reducing drug toxicity.

Published
2017
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