Modification of cap group in δ-lactam-based histone deacetylase (HDAC) inhibitors

Hwan Mook Kim; Sung Hee Hong; Myung Sook Kim; Chang Woo Lee; Jong Soon Kang; Kiho Lee; Song Kyu Park; Jeung Whan Han; Hee Yoon Lee; Yongseok Choi; Ho Jeung Kwon; Gyoonhee Han

doi:10.1016/j.bmcl.2007.09.034

Modification of cap group in δ-lactam-based histone deacetylase (HDAC) inhibitors

Hwan Mook Kim, Sung Hee Hong, Myung Sook Kim, Chang Woo Lee, Jong Soon Kang, Kiho Lee, Song Kyu Park, Jeung Whan Han, Hee Yoon Lee, Yongseok Choi, Ho Jeung Kwon, Gyoonhee Han

Department of Pharmacy

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

28 Scopus citations

Abstract

Novel δ-lactam-based HDAC inhibitors which have various substituted benzyl, bi-aromatic cap groups were prepared using ring closure metathesis reaction, and evaluated their HDAC inhibitory activities and anti-proliferative effects. Among prepared analogues, 11m and 11o have very strong HDAC enzymatic inhibition and showed the most potent growth inhibitory activity to five human tumor cell lines including PC-3, ACHN, NUGC-3, HCT-15, and MBA-MB-231 tumor cell lines. Compounds 11m and 11o also showed good tumor growth inhibition of MDA-MB-231 cells in in vivo xenograft model. Structure-activity relationship study using docking model explained the significance of hydrophobic aromatic cap groups for their in vitro activities.

Original language	English
Pages (from-to)	6234-6238
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	17
Issue number	22
DOIs	https://doi.org/10.1016/j.bmcl.2007.09.034
State	Published - 15 Nov 2007

Keywords

Anticancer chemotherapy
Docking model
Enzyme inhibitor
Growth inhibition
HDAC
Histone deacetylase
In vivo xenograft model

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmcl.2007.09.034

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title = "Modification of cap group in δ-lactam-based histone deacetylase (HDAC) inhibitors",

abstract = "Novel δ-lactam-based HDAC inhibitors which have various substituted benzyl, bi-aromatic cap groups were prepared using ring closure metathesis reaction, and evaluated their HDAC inhibitory activities and anti-proliferative effects. Among prepared analogues, 11m and 11o have very strong HDAC enzymatic inhibition and showed the most potent growth inhibitory activity to five human tumor cell lines including PC-3, ACHN, NUGC-3, HCT-15, and MBA-MB-231 tumor cell lines. Compounds 11m and 11o also showed good tumor growth inhibition of MDA-MB-231 cells in in vivo xenograft model. Structure-activity relationship study using docking model explained the significance of hydrophobic aromatic cap groups for their in vitro activities.",

keywords = "Anticancer chemotherapy, Docking model, Enzyme inhibitor, Growth inhibition, HDAC, Histone deacetylase, In vivo xenograft model",

author = "Kim, \{Hwan Mook\} and Hong, \{Sung Hee\} and Kim, \{Myung Sook\} and Lee, \{Chang Woo\} and Kang, \{Jong Soon\} and Kiho Lee and Park, \{Song Kyu\} and Han, \{Jeung Whan\} and Lee, \{Hee Yoon\} and Yongseok Choi and Kwon, \{Ho Jeung\} and Gyoonhee Han",

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doi = "10.1016/j.bmcl.2007.09.034",

language = "English",

volume = "17",

pages = "6234--6238",

journal = "Bioorganic and Medicinal Chemistry Letters",

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T1 - Modification of cap group in δ-lactam-based histone deacetylase (HDAC) inhibitors

AU - Kim, Hwan Mook

AU - Hong, Sung Hee

AU - Kim, Myung Sook

AU - Lee, Chang Woo

AU - Kang, Jong Soon

AU - Lee, Kiho

AU - Park, Song Kyu

AU - Han, Jeung Whan

AU - Lee, Hee Yoon

AU - Choi, Yongseok

AU - Kwon, Ho Jeung

AU - Han, Gyoonhee

PY - 2007/11/15

Y1 - 2007/11/15

N2 - Novel δ-lactam-based HDAC inhibitors which have various substituted benzyl, bi-aromatic cap groups were prepared using ring closure metathesis reaction, and evaluated their HDAC inhibitory activities and anti-proliferative effects. Among prepared analogues, 11m and 11o have very strong HDAC enzymatic inhibition and showed the most potent growth inhibitory activity to five human tumor cell lines including PC-3, ACHN, NUGC-3, HCT-15, and MBA-MB-231 tumor cell lines. Compounds 11m and 11o also showed good tumor growth inhibition of MDA-MB-231 cells in in vivo xenograft model. Structure-activity relationship study using docking model explained the significance of hydrophobic aromatic cap groups for their in vitro activities.

AB - Novel δ-lactam-based HDAC inhibitors which have various substituted benzyl, bi-aromatic cap groups were prepared using ring closure metathesis reaction, and evaluated their HDAC inhibitory activities and anti-proliferative effects. Among prepared analogues, 11m and 11o have very strong HDAC enzymatic inhibition and showed the most potent growth inhibitory activity to five human tumor cell lines including PC-3, ACHN, NUGC-3, HCT-15, and MBA-MB-231 tumor cell lines. Compounds 11m and 11o also showed good tumor growth inhibition of MDA-MB-231 cells in in vivo xenograft model. Structure-activity relationship study using docking model explained the significance of hydrophobic aromatic cap groups for their in vitro activities.

KW - Anticancer chemotherapy

KW - Docking model

KW - Enzyme inhibitor

KW - Growth inhibition

KW - HDAC

KW - Histone deacetylase

KW - In vivo xenograft model

UR - https://www.scopus.com/pages/publications/35148888600

U2 - 10.1016/j.bmcl.2007.09.034

DO - 10.1016/j.bmcl.2007.09.034

M3 - Article

C2 - 17904843

AN - SCOPUS:35148888600

SN - 0960-894X

VL - 17

SP - 6234

EP - 6238

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 22

ER -

Modification of cap group in δ-lactam-based histone deacetylase (HDAC) inhibitors

Abstract

Keywords

UN SDGs

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