title: Structure-activity relationship and enzyme kinetic studies on 4-aryl-1H-1,2,3-triazoles as indoleamine 2,3-dioxygenase (IDO) inhibitors.
abstract: Previously, we have reported the design and synthesis of 4-aryl-1H-1,2,3-triazoles as inhibitors of indoleamine 2,3-dioxygenase (IDO), a promising therapeutic target of cancer. Here, we present the structure-activity relationship and enzyme kinetic studies on a series of 4-aryl-1H-1,2,3-triazoles. Three compounds (1, 6, 8) were found to possess more IDO inhibitory potency than the most commonly used 1-methyltryptophan. The results from the structure-activity relationship and molecular docking studies indicated that an electron-withdrawing group with low steric hindrance near the NH group of triazoles was necessary for the IDO inhibition.
authors.affiliation: State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Handan Road 220, Shanghai 200433, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Huang
authors.forename: Maofa
authors.initials: M
authors.lastname: Zheng
authors.forename: Shuangshuang
authors.initials: S
authors.lastname: Yang
authors.forename: Chunxiang
authors.initials: C
authors.lastname: Kuang
authors.forename: Cunjing
authors.initials: C
authors.lastname: Yu
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
mesh_terms: D020134:Catalytic Domain; D049109:Cell Proliferation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D014230:Triazoles