Design, synthesis, and evaluation of hinge-binder tethered 1,2,3-triazolylsalicylamide derivatives as Aurora kinase inhibitors

Yunkyung Jeong; Jooyeon Lee; Jae Sang Ryu

doi:10.1016/j.bmc.2016.03.042

Design, synthesis, and evaluation of hinge-binder tethered 1,2,3-triazolylsalicylamide derivatives as Aurora kinase inhibitors

Yunkyung Jeong, Jooyeon Lee, Jae Sang Ryu

Department of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

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.

Original language	English
Pages (from-to)	2114-2124
Number of pages	11
Journal	Bioorganic and Medicinal Chemistry
Volume	24
Issue number	9
DOIs	https://doi.org/10.1016/j.bmc.2016.03.042
State	Published - 1 May 2016

Bibliographical note

Funding Information:
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF- 2015R1A2A2A01004511 ).

Publisher Copyright:
© 2016 Elsevier Ltd. All rights reserved.

Keywords

1,2,3-Triazole
Anticancer
Aurora kinase
Click chemistry
Hinge-binder

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10.1016/j.bmc.2016.03.042

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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.",

keywords = "1,2,3-Triazole, Anticancer, Aurora kinase, Click chemistry, Hinge-binder",

author = "Yunkyung Jeong and Jooyeon Lee and Ryu, {Jae Sang}",

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AU - Ryu, Jae Sang

N1 - Funding Information: This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF- 2015R1A2A2A01004511 ). Publisher Copyright: © 2016 Elsevier Ltd. All rights reserved.

PY - 2016/5/1

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N2 - 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.

AB - 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.

KW - 1,2,3-Triazole

KW - Anticancer

KW - Aurora kinase

KW - Click chemistry

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ER -

Design, synthesis, and evaluation of hinge-binder tethered 1,2,3-triazolylsalicylamide derivatives as Aurora kinase inhibitors

Abstract

Bibliographical note

Keywords

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