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

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

26 Citations (Scopus)

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
Publication status	Published - 2007 Nov 15

Bibliographical note

Funding Information:
This research was partly supported by a grant from KRIBB Research Initiative program, a Grant (0405-NS01-0704-0001) of the Korean Health 21 R&D Project, Ministry of Health and Welfare, and the Brain Korea 21 project the Republic of Korea.

All Science Journal Classification (ASJC) codes

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

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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.",

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",

note = "Funding Information: This research was partly supported by a grant from KRIBB Research Initiative program, a Grant (0405-NS01-0704-0001) of the Korean Health 21 R&D Project, Ministry of Health and Welfare, and the Brain Korea 21 project the Republic of Korea. ",

year = "2007",

month = nov,

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

language = "English",

volume = "17",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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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

N1 - Funding Information: This research was partly supported by a grant from KRIBB Research Initiative program, a Grant (0405-NS01-0704-0001) of the Korean Health 21 R&D Project, Ministry of Health and Welfare, and the Brain Korea 21 project the Republic of Korea.

PY - 2007/11/15

Y1 - 2007/11/15

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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.

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

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

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