Studies of Coumarin Derivatives for Constitutive Androstane Receptor (CAR) Activation

Constitutive androstane receptor (CAR) activation has found to ameliorate diabetes in animal models. However, no CAR agonists are available clinically. Therefore, a safe and effective CAR activator would be an alternative option. In this study, sixty courmarin derivatives either synthesized or purif...
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Autor*in:	Shin-Hun Juang [verfasserIn] Min-Tsang Hsieh [verfasserIn] Pei-Ling Hsu [verfasserIn] Ju-Ling Chen [verfasserIn] Hui-Kang Liu [verfasserIn] Fong-Pin Liang [verfasserIn] Sheng-Chu Kuo [verfasserIn] Chen-Yuan Chiu [verfasserIn] Shing-Hwa Liu [verfasserIn] Chen-Hsi Chou [verfasserIn] Tian-Shung Wu [verfasserIn] Hsin-Yi Hung [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2020

Schlagwörter:	Yin Chen Hao constitutive androstane receptor coumarin scoparone

Übergeordnetes Werk:	In: Molecules - MDPI AG, 2003, 26(2020), 1, p 164
Übergeordnetes Werk:	volume:26 ; year:2020 ; number:1, p 164

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/molecules26010164

Katalog-ID:	DOAJ084842253

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520			\|a Constitutive androstane receptor (CAR) activation has found to ameliorate diabetes in animal models. However, no CAR agonists are available clinically. Therefore, a safe and effective CAR activator would be an alternative option. In this study, sixty courmarin derivatives either synthesized or purified from <i<Artemisia capillaris</i< were screened for CAR activation activity. Chemical modifications were on position 5,6,7,8 with mono-, di-, tri-, or tetra-substitutions. Among all the compounds subjected for in vitro CAR activation screening, 6,7-diprenoxycoumarin was the most effective and was selected for further preclinical studies. Chemical modification on the 6 position and unsaturated chains were generally beneficial. Electron-withdrawn groups as well as long unsaturated chains were hazardous to the activity. Mechanism of action studies showed that CAR activation of 6,7-diprenoxycoumarin might be through the inhibition of EGFR signaling and upregulating PP2Ac methylation. To sum up, modification mimicking natural occurring coumarins shed light on CAR studies and the established screening system provides a rapid method for the discovery and development of CAR activators. In addition, one CAR activator, scoparone, did showed anti-diabetes effect in <i<db</i</<i<db</i< mice without elevation of insulin levels.
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allfieldsSound	10.3390/molecules26010164 doi (DE-627)DOAJ084842253 (DE-599)DOAJ30bfc32eb7534be8a4d05ff37022e91c DE-627 ger DE-627 rakwb eng QD241-441 Shin-Hun Juang verfasserin aut Studies of Coumarin Derivatives for Constitutive Androstane Receptor (CAR) Activation 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Constitutive androstane receptor (CAR) activation has found to ameliorate diabetes in animal models. However, no CAR agonists are available clinically. Therefore, a safe and effective CAR activator would be an alternative option. In this study, sixty courmarin derivatives either synthesized or purified from <i<Artemisia capillaris</i< were screened for CAR activation activity. Chemical modifications were on position 5,6,7,8 with mono-, di-, tri-, or tetra-substitutions. Among all the compounds subjected for in vitro CAR activation screening, 6,7-diprenoxycoumarin was the most effective and was selected for further preclinical studies. Chemical modification on the 6 position and unsaturated chains were generally beneficial. Electron-withdrawn groups as well as long unsaturated chains were hazardous to the activity. Mechanism of action studies showed that CAR activation of 6,7-diprenoxycoumarin might be through the inhibition of EGFR signaling and upregulating PP2Ac methylation. To sum up, modification mimicking natural occurring coumarins shed light on CAR studies and the established screening system provides a rapid method for the discovery and development of CAR activators. In addition, one CAR activator, scoparone, did showed anti-diabetes effect in <i<db</i</<i<db</i< mice without elevation of insulin levels. Yin Chen Hao constitutive androstane receptor coumarin scoparone Organic chemistry Min-Tsang Hsieh verfasserin aut Pei-Ling Hsu verfasserin aut Ju-Ling Chen verfasserin aut Hui-Kang Liu verfasserin aut Fong-Pin Liang verfasserin aut Sheng-Chu Kuo verfasserin aut Chen-Yuan Chiu verfasserin aut Shing-Hwa Liu verfasserin aut Chen-Hsi Chou verfasserin aut Tian-Shung Wu verfasserin aut Hsin-Yi Hung verfasserin aut In Molecules MDPI AG, 2003 26(2020), 1, p 164 (DE-627)311313132 (DE-600)2008644-1 14203049 nnns volume:26 year:2020 number:1, p 164 https://doi.org/10.3390/molecules26010164 kostenfrei https://doaj.org/article/30bfc32eb7534be8a4d05ff37022e91c kostenfrei https://www.mdpi.com/1420-3049/26/1/164 kostenfrei https://doaj.org/toc/1420-3049 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 26 2020 1, p 164
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callnumber-first	Q - Science
author	Shin-Hun Juang
spellingShingle	Shin-Hun Juang misc QD241-441 misc Yin Chen Hao misc constitutive androstane receptor misc coumarin misc scoparone misc Organic chemistry Studies of Coumarin Derivatives for Constitutive Androstane Receptor (CAR) Activation
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topic_title	QD241-441 Studies of Coumarin Derivatives for Constitutive Androstane Receptor (CAR) Activation Yin Chen Hao constitutive androstane receptor coumarin scoparone
topic	misc QD241-441 misc Yin Chen Hao misc constitutive androstane receptor misc coumarin misc scoparone misc Organic chemistry
topic_unstemmed	misc QD241-441 misc Yin Chen Hao misc constitutive androstane receptor misc coumarin misc scoparone misc Organic chemistry
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title	Studies of Coumarin Derivatives for Constitutive Androstane Receptor (CAR) Activation
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title_full	Studies of Coumarin Derivatives for Constitutive Androstane Receptor (CAR) Activation
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author_browse	Shin-Hun Juang Min-Tsang Hsieh Pei-Ling Hsu Ju-Ling Chen Hui-Kang Liu Fong-Pin Liang Sheng-Chu Kuo Chen-Yuan Chiu Shing-Hwa Liu Chen-Hsi Chou Tian-Shung Wu Hsin-Yi Hung
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title_sort	studies of coumarin derivatives for constitutive androstane receptor (car) activation
callnumber	QD241-441
title_auth	Studies of Coumarin Derivatives for Constitutive Androstane Receptor (CAR) Activation
abstract	Constitutive androstane receptor (CAR) activation has found to ameliorate diabetes in animal models. However, no CAR agonists are available clinically. Therefore, a safe and effective CAR activator would be an alternative option. In this study, sixty courmarin derivatives either synthesized or purified from <i<Artemisia capillaris</i< were screened for CAR activation activity. Chemical modifications were on position 5,6,7,8 with mono-, di-, tri-, or tetra-substitutions. Among all the compounds subjected for in vitro CAR activation screening, 6,7-diprenoxycoumarin was the most effective and was selected for further preclinical studies. Chemical modification on the 6 position and unsaturated chains were generally beneficial. Electron-withdrawn groups as well as long unsaturated chains were hazardous to the activity. Mechanism of action studies showed that CAR activation of 6,7-diprenoxycoumarin might be through the inhibition of EGFR signaling and upregulating PP2Ac methylation. To sum up, modification mimicking natural occurring coumarins shed light on CAR studies and the established screening system provides a rapid method for the discovery and development of CAR activators. In addition, one CAR activator, scoparone, did showed anti-diabetes effect in <i<db</i</<i<db</i< mice without elevation of insulin levels.
abstractGer	Constitutive androstane receptor (CAR) activation has found to ameliorate diabetes in animal models. However, no CAR agonists are available clinically. Therefore, a safe and effective CAR activator would be an alternative option. In this study, sixty courmarin derivatives either synthesized or purified from <i<Artemisia capillaris</i< were screened for CAR activation activity. Chemical modifications were on position 5,6,7,8 with mono-, di-, tri-, or tetra-substitutions. Among all the compounds subjected for in vitro CAR activation screening, 6,7-diprenoxycoumarin was the most effective and was selected for further preclinical studies. Chemical modification on the 6 position and unsaturated chains were generally beneficial. Electron-withdrawn groups as well as long unsaturated chains were hazardous to the activity. Mechanism of action studies showed that CAR activation of 6,7-diprenoxycoumarin might be through the inhibition of EGFR signaling and upregulating PP2Ac methylation. To sum up, modification mimicking natural occurring coumarins shed light on CAR studies and the established screening system provides a rapid method for the discovery and development of CAR activators. In addition, one CAR activator, scoparone, did showed anti-diabetes effect in <i<db</i</<i<db</i< mice without elevation of insulin levels.
abstract_unstemmed	Constitutive androstane receptor (CAR) activation has found to ameliorate diabetes in animal models. However, no CAR agonists are available clinically. Therefore, a safe and effective CAR activator would be an alternative option. In this study, sixty courmarin derivatives either synthesized or purified from <i<Artemisia capillaris</i< were screened for CAR activation activity. Chemical modifications were on position 5,6,7,8 with mono-, di-, tri-, or tetra-substitutions. Among all the compounds subjected for in vitro CAR activation screening, 6,7-diprenoxycoumarin was the most effective and was selected for further preclinical studies. Chemical modification on the 6 position and unsaturated chains were generally beneficial. Electron-withdrawn groups as well as long unsaturated chains were hazardous to the activity. Mechanism of action studies showed that CAR activation of 6,7-diprenoxycoumarin might be through the inhibition of EGFR signaling and upregulating PP2Ac methylation. To sum up, modification mimicking natural occurring coumarins shed light on CAR studies and the established screening system provides a rapid method for the discovery and development of CAR activators. In addition, one CAR activator, scoparone, did showed anti-diabetes effect in <i<db</i</<i<db</i< mice without elevation of insulin levels.
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container_issue	1, p 164
title_short	Studies of Coumarin Derivatives for Constitutive Androstane Receptor (CAR) Activation
url	https://doi.org/10.3390/molecules26010164 https://doaj.org/article/30bfc32eb7534be8a4d05ff37022e91c https://www.mdpi.com/1420-3049/26/1/164 https://doaj.org/toc/1420-3049
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author2	Min-Tsang Hsieh Pei-Ling Hsu Ju-Ling Chen Hui-Kang Liu Fong-Pin Liang Sheng-Chu Kuo Chen-Yuan Chiu Shing-Hwa Liu Chen-Hsi Chou Tian-Shung Wu Hsin-Yi Hung
author2Str	Min-Tsang Hsieh Pei-Ling Hsu Ju-Ling Chen Hui-Kang Liu Fong-Pin Liang Sheng-Chu Kuo Chen-Yuan Chiu Shing-Hwa Liu Chen-Hsi Chou Tian-Shung Wu Hsin-Yi Hung
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doi_str	10.3390/molecules26010164
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up_date	2024-07-04T00:47:09.531Z
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To sum up, modification mimicking natural occurring coumarins shed light on CAR studies and the established screening system provides a rapid method for the discovery and development of CAR activators. 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Studies of Coumarin Derivatives for Constitutive Androstane Receptor (CAR) Activation

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