Search for a novel SIRT1 activator: Structural modification of SRT1720 and biological evaluation

Yuji Matsuya; Yuta Kobayashi; Sayumi Uchida; Yukihiro Itoh; Hideyuki Sawada; Takayoshi Suzuki; Naoki Miyata; Kenji Sugimoto; Naoki Toyooka

doi:10.1016/j.bmcl.2013.06.070

Search for a novel SIRT1 activator: Structural modification of SRT1720 and biological evaluation

Yuji Matsuya^*, Yuta Kobayashi, Sayumi Uchida, Yukihiro Itoh, Hideyuki Sawada, Takayoshi Suzuki, Naoki Miyata, Kenji Sugimoto, Naoki Toyooka

^*Corresponding author for this work

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

15 Scopus citations

Abstract

Syntheses and biological evaluation of novel SRT1720 derivatives are described in search for new candidates of SIRT1 activator. Several parts of the SRT1720 structure, including piperazine moiety, quinoxaline ring on the amide group, and position of the amide function, were modified, and the assay results indicated that transfer of the ortho amide-substituent regarding to the imidazo[1,2-b]thiazole core onto the meta position resulted in improvement of SIRT1 activation ability. Modeling analyses of SRT1720 and the most potent derivative bound to model complex of SIRT1 with peptide substrate were also performed.

Original language	English
Pages (from-to)	4907-4910
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	23
Issue number	17
DOIs	https://doi.org/10.1016/j.bmcl.2013.06.070
State	Published - 2013/09/01

Keywords

Chemical synthesis
Docking study
Structural modification

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2013.06.070

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title = "Search for a novel SIRT1 activator: Structural modification of SRT1720 and biological evaluation",

abstract = "Syntheses and biological evaluation of novel SRT1720 derivatives are described in search for new candidates of SIRT1 activator. Several parts of the SRT1720 structure, including piperazine moiety, quinoxaline ring on the amide group, and position of the amide function, were modified, and the assay results indicated that transfer of the ortho amide-substituent regarding to the imidazo[1,2-b]thiazole core onto the meta position resulted in improvement of SIRT1 activation ability. Modeling analyses of SRT1720 and the most potent derivative bound to model complex of SIRT1 with peptide substrate were also performed.",

keywords = "Chemical synthesis, Docking study, Structural modification",

author = "Yuji Matsuya and Yuta Kobayashi and Sayumi Uchida and Yukihiro Itoh and Hideyuki Sawada and Takayoshi Suzuki and Naoki Miyata and Kenji Sugimoto and Naoki Toyooka",

year = "2013",

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doi = "10.1016/j.bmcl.2013.06.070",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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TY - JOUR

T1 - Search for a novel SIRT1 activator

T2 - Structural modification of SRT1720 and biological evaluation

AU - Matsuya, Yuji

AU - Kobayashi, Yuta

AU - Uchida, Sayumi

AU - Itoh, Yukihiro

AU - Sawada, Hideyuki

AU - Suzuki, Takayoshi

AU - Miyata, Naoki

AU - Sugimoto, Kenji

AU - Toyooka, Naoki

PY - 2013/9/1

Y1 - 2013/9/1

N2 - Syntheses and biological evaluation of novel SRT1720 derivatives are described in search for new candidates of SIRT1 activator. Several parts of the SRT1720 structure, including piperazine moiety, quinoxaline ring on the amide group, and position of the amide function, were modified, and the assay results indicated that transfer of the ortho amide-substituent regarding to the imidazo[1,2-b]thiazole core onto the meta position resulted in improvement of SIRT1 activation ability. Modeling analyses of SRT1720 and the most potent derivative bound to model complex of SIRT1 with peptide substrate were also performed.

AB - Syntheses and biological evaluation of novel SRT1720 derivatives are described in search for new candidates of SIRT1 activator. Several parts of the SRT1720 structure, including piperazine moiety, quinoxaline ring on the amide group, and position of the amide function, were modified, and the assay results indicated that transfer of the ortho amide-substituent regarding to the imidazo[1,2-b]thiazole core onto the meta position resulted in improvement of SIRT1 activation ability. Modeling analyses of SRT1720 and the most potent derivative bound to model complex of SIRT1 with peptide substrate were also performed.

KW - Chemical synthesis

KW - Docking study

KW - Structural modification

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U2 - 10.1016/j.bmcl.2013.06.070

DO - 10.1016/j.bmcl.2013.06.070

M3 - 学術論文

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AN - SCOPUS:84881376738

SN - 0960-894X

VL - 23

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JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 17

ER -

Search for a novel SIRT1 activator: Structural modification of SRT1720 and biological evaluation

Abstract

Keywords

ASJC Scopus subject areas

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