Halogenated analogs of 1′-acetoxychavicol acetate, Rev-export inhibitor from Alpinia galanga, designed from mechanism of action

Satoru Tamura; Atsushi Shiomi; Tominori Kimura; Nobutoshi Murakami

doi:10.1016/j.bmcl.2010.02.070

Halogenated analogs of 1′-acetoxychavicol acetate, Rev-export inhibitor from Alpinia galanga, designed from mechanism of action

Satoru Tamura, Atsushi Shiomi, Tominori Kimura, Nobutoshi Murakami

SCI - Chemistry

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

14 Citations (Scopus)

Abstract

In the course of search for the robust analogs of 1′-acetoxychavicol acetate (ACA, 1), the Rev-export inhibitor from the medicinal plant Alpinia galanga, we clarified formation of the quinone methide intermediate ii to be essential for exerting the inhibitory activity of 1. Based on this mechanism of action, the rational design from the MO calculation of the conclusive activation energy to ii resulted in the four halogenated analogs with more potent activity than ACA (1). In particular, the difluoroanalog 20d exhibited approximately four-fold potent activity as compared with 1.

Original language	English
Pages (from-to)	2082-2085
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	20
Issue number	7
DOIs	https://doi.org/10.1016/j.bmcl.2010.02.070
Publication status	Published - 2010 Apr 1

Keywords

1′-Acetoxychavicol acetate
Evidence-based design
Halogenated analog
Quinone methide
Rev-export inhibitor

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.2010.02.070

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title = "Halogenated analogs of 1′-acetoxychavicol acetate, Rev-export inhibitor from Alpinia galanga, designed from mechanism of action",

abstract = "In the course of search for the robust analogs of 1′-acetoxychavicol acetate (ACA, 1), the Rev-export inhibitor from the medicinal plant Alpinia galanga, we clarified formation of the quinone methide intermediate ii to be essential for exerting the inhibitory activity of 1. Based on this mechanism of action, the rational design from the MO calculation of the conclusive activation energy to ii resulted in the four halogenated analogs with more potent activity than ACA (1). In particular, the difluoroanalog 20d exhibited approximately four-fold potent activity as compared with 1.",

keywords = "1′-Acetoxychavicol acetate, Evidence-based design, Halogenated analog, Quinone methide, Rev-export inhibitor",

author = "Satoru Tamura and Atsushi Shiomi and Tominori Kimura and Nobutoshi Murakami",

note = "Funding Information: We wish to thank Professor Minoru Yoshida in RIKEN Advanced Science Institute for giving the fission yeast S. pombe. This work was supported in part by Grants-in-Aid for Scientific Research (Grant No. 19590100 ) from the Ministry of Education, Science, Culture and Sports. The authors are grateful to the Shorai Foundation for Science and Technology for financial support.",

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doi = "10.1016/j.bmcl.2010.02.070",

language = "English",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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T1 - Halogenated analogs of 1′-acetoxychavicol acetate, Rev-export inhibitor from Alpinia galanga, designed from mechanism of action

AU - Tamura, Satoru

AU - Shiomi, Atsushi

AU - Kimura, Tominori

AU - Murakami, Nobutoshi

N1 - Funding Information: We wish to thank Professor Minoru Yoshida in RIKEN Advanced Science Institute for giving the fission yeast S. pombe. This work was supported in part by Grants-in-Aid for Scientific Research (Grant No. 19590100 ) from the Ministry of Education, Science, Culture and Sports. The authors are grateful to the Shorai Foundation for Science and Technology for financial support.

PY - 2010/4/1

Y1 - 2010/4/1

N2 - In the course of search for the robust analogs of 1′-acetoxychavicol acetate (ACA, 1), the Rev-export inhibitor from the medicinal plant Alpinia galanga, we clarified formation of the quinone methide intermediate ii to be essential for exerting the inhibitory activity of 1. Based on this mechanism of action, the rational design from the MO calculation of the conclusive activation energy to ii resulted in the four halogenated analogs with more potent activity than ACA (1). In particular, the difluoroanalog 20d exhibited approximately four-fold potent activity as compared with 1.

AB - In the course of search for the robust analogs of 1′-acetoxychavicol acetate (ACA, 1), the Rev-export inhibitor from the medicinal plant Alpinia galanga, we clarified formation of the quinone methide intermediate ii to be essential for exerting the inhibitory activity of 1. Based on this mechanism of action, the rational design from the MO calculation of the conclusive activation energy to ii resulted in the four halogenated analogs with more potent activity than ACA (1). In particular, the difluoroanalog 20d exhibited approximately four-fold potent activity as compared with 1.

KW - 1′-Acetoxychavicol acetate

KW - Evidence-based design

KW - Halogenated analog

KW - Quinone methide

KW - Rev-export inhibitor

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DO - 10.1016/j.bmcl.2010.02.070

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JF - Bioorganic and Medicinal Chemistry Letters

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ER -

Halogenated analogs of 1′-acetoxychavicol acetate, Rev-export inhibitor from Alpinia galanga, designed from mechanism of action

Abstract

Keywords

ASJC Scopus subject areas

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