Synthesis and pharmacological evaluation of new methyloxiranylmethoxyxanthone analogues

Sangwook Woo; Da Hye Kang; Jung Min Nam; Chong Soon Lee; Eun Mi Ha; Eung Seok Lee; Youngjoo Kwon; Younghwa Na

doi:10.1016/j.ejmech.2010.06.017

Synthesis and pharmacological evaluation of new methyloxiranylmethoxyxanthone analogues

Sangwook Woo, Da Hye Kang, Jung Min Nam, Chong Soon Lee, Eun Mi Ha, Eung Seok Lee, Youngjoo Kwon, Younghwa Na

Department of Pharmaceutical Sciences

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

20 Scopus citations

Abstract

In order to develop potential anti-cancer agents that act on topoisomerase II and DNA, we have synthesized 12 new xanthone derivatives. In the cytotoxicity test, compounds 17 and 31 exhibited 2- to 7-fold stronger inhibitory activity than adriamycin against most cancer cell lines tested. Halohydrin group-tethered compounds 19, 21 and 27 showed comparable topoisomerase II inhibitory activity to etoposide at 100 μM concentration. In the DNA cross-linking test, compounds 20, 30 and 31 produced DNA cross-linked adducts and compound 30 was the strongest DNA cross-linker. Based on the combined pharmacological results, we suspected that the strong anti-cancer activity of compounds 16, 17, 20, 30 and 31 originated from the DNA mono-alkylation or cross-linking properties of the compounds. In order to develop potential anti-cancer agents that act on topoisomerase II and DNA, we have synthesized 12 new xanthone derivatives.

Original language	English
Pages (from-to)	4221-4228
Number of pages	8
Journal	European Journal of Medicinal Chemistry
Volume	45
Issue number	9
DOIs	https://doi.org/10.1016/j.ejmech.2010.06.017
State	Published - Sep 2010

Bibliographical note

Funding Information:
This work was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD) ( KRF-2006-521-E00159 ). J.M.N. was partially supported by the Brain Korea 21 project.

Keywords

Anticancer activities
DNA cross-linking
Methyloxiranylmethoxyxanthones
Oxiranylmethoxyxanthones
Topoisomerase II inhibition

UN SDGs

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

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10.1016/j.ejmech.2010.06.017

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title = "Synthesis and pharmacological evaluation of new methyloxiranylmethoxyxanthone analogues",

abstract = "In order to develop potential anti-cancer agents that act on topoisomerase II and DNA, we have synthesized 12 new xanthone derivatives. In the cytotoxicity test, compounds 17 and 31 exhibited 2- to 7-fold stronger inhibitory activity than adriamycin against most cancer cell lines tested. Halohydrin group-tethered compounds 19, 21 and 27 showed comparable topoisomerase II inhibitory activity to etoposide at 100 μM concentration. In the DNA cross-linking test, compounds 20, 30 and 31 produced DNA cross-linked adducts and compound 30 was the strongest DNA cross-linker. Based on the combined pharmacological results, we suspected that the strong anti-cancer activity of compounds 16, 17, 20, 30 and 31 originated from the DNA mono-alkylation or cross-linking properties of the compounds. In order to develop potential anti-cancer agents that act on topoisomerase II and DNA, we have synthesized 12 new xanthone derivatives.",

keywords = "Anticancer activities, DNA cross-linking, Methyloxiranylmethoxyxanthones, Oxiranylmethoxyxanthones, Topoisomerase II inhibition",

author = "Sangwook Woo and Kang, {Da Hye} and Nam, {Jung Min} and Lee, {Chong Soon} and Ha, {Eun Mi} and Lee, {Eung Seok} and Youngjoo Kwon and Younghwa Na",

note = "Funding Information: This work was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD) ( KRF-2006-521-E00159 ). J.M.N. was partially supported by the Brain Korea 21 project.",

year = "2010",

month = sep,

doi = "10.1016/j.ejmech.2010.06.017",

language = "English",

volume = "45",

pages = "4221--4228",

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T1 - Synthesis and pharmacological evaluation of new methyloxiranylmethoxyxanthone analogues

AU - Woo, Sangwook

AU - Kang, Da Hye

AU - Nam, Jung Min

AU - Lee, Chong Soon

AU - Ha, Eun Mi

AU - Lee, Eung Seok

AU - Kwon, Youngjoo

AU - Na, Younghwa

N1 - Funding Information: This work was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD) ( KRF-2006-521-E00159 ). J.M.N. was partially supported by the Brain Korea 21 project.

PY - 2010/9

Y1 - 2010/9

N2 - In order to develop potential anti-cancer agents that act on topoisomerase II and DNA, we have synthesized 12 new xanthone derivatives. In the cytotoxicity test, compounds 17 and 31 exhibited 2- to 7-fold stronger inhibitory activity than adriamycin against most cancer cell lines tested. Halohydrin group-tethered compounds 19, 21 and 27 showed comparable topoisomerase II inhibitory activity to etoposide at 100 μM concentration. In the DNA cross-linking test, compounds 20, 30 and 31 produced DNA cross-linked adducts and compound 30 was the strongest DNA cross-linker. Based on the combined pharmacological results, we suspected that the strong anti-cancer activity of compounds 16, 17, 20, 30 and 31 originated from the DNA mono-alkylation or cross-linking properties of the compounds. In order to develop potential anti-cancer agents that act on topoisomerase II and DNA, we have synthesized 12 new xanthone derivatives.

AB - In order to develop potential anti-cancer agents that act on topoisomerase II and DNA, we have synthesized 12 new xanthone derivatives. In the cytotoxicity test, compounds 17 and 31 exhibited 2- to 7-fold stronger inhibitory activity than adriamycin against most cancer cell lines tested. Halohydrin group-tethered compounds 19, 21 and 27 showed comparable topoisomerase II inhibitory activity to etoposide at 100 μM concentration. In the DNA cross-linking test, compounds 20, 30 and 31 produced DNA cross-linked adducts and compound 30 was the strongest DNA cross-linker. Based on the combined pharmacological results, we suspected that the strong anti-cancer activity of compounds 16, 17, 20, 30 and 31 originated from the DNA mono-alkylation or cross-linking properties of the compounds. In order to develop potential anti-cancer agents that act on topoisomerase II and DNA, we have synthesized 12 new xanthone derivatives.

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KW - DNA cross-linking

KW - Methyloxiranylmethoxyxanthones

KW - Oxiranylmethoxyxanthones

KW - Topoisomerase II inhibition

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Synthesis and pharmacological evaluation of new methyloxiranylmethoxyxanthone analogues

Abstract

Bibliographical note

Keywords

UN SDGs

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