title: Click approach to the discovery of 1,2,3-triazolylsalicylamides as potent Aurora kinase inhibitors.
abstract: A series of 1,2,3-triazolylsalicylamide derivatives has been developed from the antiproliferative agent 7 and was evaluated for their Aurora kinase inhibitory activity. The novel 1,2,3-triazolylsalicylamide scaffold could be readily assembled by Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition, allowing rapid access to the structurally diverse analogues. The synthesized 1,2,3-triazolylsalicylamide derivatives revealed a significant Aurora kinase inhibitory activity. In particular, 8g inhibited Aurora A with IC50 values of 0.37μM. The critical role of phenolic -OH in the binding was confirmed by a molecular modeling study.
authors.affiliation: College of Pharmacy & Graduate School of Pharmaceutical Sciences, Global Top 5 Research Program, Ewha Womans University, 11-1 Daehyun-Dong, Seodaemun-Gu, Seoul 120-750, Republic of Korea.
authors.forename: Doohee
authors.initials: D
authors.lastname: Song
authors.affiliation: College of Pharmacy & Graduate School of Pharmaceutical Sciences, Global Top 5 Research Program, Ewha Womans University, 11-1 Daehyun-Dong, Seodaemun-Gu, Seoul 120-750, Republic of Korea.
authors.forename: Yunjeong
authors.initials: Y
authors.lastname: Park
authors.affiliation: College of Pharmacy & Graduate School of Pharmaceutical Sciences, Global Top 5 Research Program, Ewha Womans University, 11-1 Daehyun-Dong, Seodaemun-Gu, Seoul 120-750, Republic of Korea.
authors.forename: Jieun
authors.initials: J
authors.lastname: Yoon
authors.affiliation: Department of Pharmacy, College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Kyeonggi-do 426-791, Republic of Korea.
authors.forename: Waqar
authors.initials: W
authors.lastname: Aman
authors.affiliation: Department of Pharmacy, College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Kyeonggi-do 426-791, Republic of Korea.
authors.forename: Jung-Mi
authors.initials: JM
authors.lastname: Hah
authors.affiliation: College of Pharmacy & Graduate School of Pharmaceutical Sciences, Global Top 5 Research Program, Ewha Womans University, 11-1 Daehyun-Dong, Seodaemun-Gu, Seoul 120-750, 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* / Q000378:metabolism; D064107:Aurora Kinase B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D057930:Click Chemistry; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012457:Salicylamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D047428:Protein Kinase Inhibitors; D012457:Salicylamides; D014230:Triazoles; C000596458:methyl 3-(5-(4-(3,5-dimethoxyphenyl)-1H-1,2,3-triazol-1-yl)-2-hydroxybenzamido)benzoate; C576917:AURKA protein, human; D064096:Aurora Kinase A; D064107:Aurora Kinase B
keywords: 1,2,3-Triazole; Anticancer; Aurora kinase; Click chemistry; Library