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The Design, Structu...
The Design, Structure–Activity, and Kinetic Studies of 3-Benzyl-5-oxa-1,2,3,4-Tetrahydro-2H-chromeno-(3,4-c)pyridin-8-yl Sulfamates as Steroid Sulfatase Inhibitors
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Chang, Chiao-Nien (författare)
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Lin, I-Chun (författare)
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Lin, Tzung-Sheng (författare)
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Chiu, Pei-Fang (författare)
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Lu, Yeh-Lin (författare)
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Narwane, Manmath (författare)
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Liu, I-Chen (författare)
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Hng, Yue (författare)
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Tsai, Keng-Chang (författare)
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Lin, Mei-Hsiang (författare)
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- Hsieh, Yves S. Y. (författare)
- KTH,Glykovetenskap,School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan
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Chen, Mei-Jou (författare)
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Liang, Pi-Hui (författare)
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(creator_code:org_t)
- Elsevier BV, 2022
- 2022
- Engelska.
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Ingår i: Bioorganic chemistry. - : Elsevier BV. - 0045-2068.
- Relaterad länk:
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https://www.scienced...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Steroid sulfatase inhibitors block the local production of estrogenic steroids and are attractive agents for the treatment of estrogen-dependent cancers. Inspiration of coumarin-based inhibitors, we synthesized thirty-two 5-oxa-1,2,3,4-tetrahydro-2H-chromeno-(3,4-c)pyridin-8-yl sulfamates, focusing on the substitution derivatives on the adjacent phenyl ring and evaluated their abilities to block STS from human placenta and MCF-7 cells. SAR analysis revealed that the incorporation of chlorine at either meta and/or para position of the adjacent phenyl ring of the tricyclic skeleton enhanced STS inhibition. Di-substitutions at the adjacent phenyl ring were superior to mono and tri-substitutions. Further kinetic analysis of these compounds revealed that chloride-bearing compounds, such as 19m, 19v, and 19w, had KI of 0.02 to 0.11 nM and kinact/KI ratios of 8.8-17.5 nM-1min-1, a parameter indicated for the efficiency of irreversible inhibition. We also used the docking model to illustrate the difference in STS inhibitory potency of compounds. Finally, the safety and anti-cancer activity of selected compounds 19m, 19v, and 19w were also studied, showing the results of low cytotoxicity on NHDF cell line and being more potent than irosustat on ZR-75-1 cell, which was a hormone-dependent cancer cell line with high STS expression.
Ämnesord
- NATURVETENSKAP -- Kemi -- Organisk kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Organic Chemistry (hsv//eng)
Nyckelord
- Steroid Sulfatase
- Sulfamate
- Hormone dependent cancer
- Irreversible Inhibitors
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Till lärosätets databas
- Av författaren/redakt...
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Chang, Chiao-Nie ...
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Lin, I-Chun
-
Lin, Tzung-Sheng
-
Chiu, Pei-Fang
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Lu, Yeh-Lin
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Narwane, Manmath
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visa fler...
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Liu, I-Chen
-
Hng, Yue
-
Tsai, Keng-Chang
-
Lin, Mei-Hsiang
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Hsieh, Yves S. Y ...
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Chen, Mei-Jou
-
Liang, Pi-Hui
-
visa färre...
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- NATURVETENSKAP
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NATURVETENSKAP
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och Kemi
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och Organisk kemi
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Bioorganic chemi ...
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Kungliga Tekniska Högskolan