title: Design, synthesis, and evaluation of hinge-binder tethered 1,2,3-triazolylsalicylamide derivatives as Aurora kinase inhibitors.
abstract: A series of hinge-binder tethered 1,2,3-triazolylsalicylamide derivatives were designed, synthesized, and evaluated for the Aurora kinase inhibitory activities. The novel hinge-binder tethered 1,2,3-triazolylsalicylamide scaffold was effectively assembled by Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC). A variety of alkynes with hinge binders were used to search proper structures-binding relationship to the hinge region. The synthesized 1,2,3-triazolylsalicylamide derivatives showed significant Aurora kinase inhibitory activity. In particular, 8a inhibited Aurora A kinase with an IC50 value of 0.284 μM, whereas 8m inhibited Aurora B kinase with an IC50 value of 0.364 μM.
authors.affiliation: College of Pharmacy & Graduate School of Pharmaceutical Sciences, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 03760, Republic of Korea.
authors.forename: Yunkyung
authors.initials: Y
authors.lastname: Jeong
authors.affiliation: College of Pharmacy & Graduate School of Pharmaceutical Sciences, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 03760, Republic of Korea.
authors.forename: Jooyeon
authors.initials: J
authors.lastname: Lee
authors.affiliation: College of Pharmacy & Graduate School of Pharmaceutical Sciences, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 03760, Republic of Korea. Electronic address: ryuj@ewha.ac.kr.
authors.forename: Jae-Sang
authors.initials: JS
authors.lastname: Ryu
mesh_terms: D064096:Aurora Kinase A / Q000037:antagonists & inhibitors*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D012457:Salicylamides / Q000494:pharmacology*
chemical_list: D047428:Protein Kinase Inhibitors; D012457:Salicylamides; D064096:Aurora Kinase A; C031060:salicylamide
keywords: 1,2,3-Triazole; Anticancer; Aurora kinase; Click chemistry; Hinge-binder