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

Korea Research Institute of Bioscience and Biotechnology
Yonsei University
Korea Advanced Institute of Science and Technology
Korea University

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

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

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

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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",

year = "2007",

month = nov,

day = "15",

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

UN SDGs

Keywords

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