Exploring the tetrahydroisoquinoline thiohydantoin scaffold blockade the androgen receptor as potent anti-prostate cancer agents
Copyright © 2017 Elsevier Masson SAS. All rights reserved..
Prostate cancer (PC) is a major cause of cancer-related male death in worldwide and the identification of new and improved potent anti-PC molecules is constantly required. A novel scaffold of tetrahydroisoquinoline thiohydantoin was rationally designed based on the enzalutamide structures and our pre-work, leading to the discovery of a series of new antiproliferative compounds. Several new analogues displayed improved androgen receptor (AR) antagonistic activity, while maintaining the higher selective toxicity toward LNCaP cells (AR-rich) versus DU145 cells (AR-deficient) compared to enzalutamide. In fact, compound 55 exhibited promising in vitro antitumor activity by impairing AR unclear translocation. More importantly, 55 showed better pharmacokinetic properties compared to the compound 1 reported in our pre-work. These results demonstrate a step towards the development of novel and improved AR antagonists.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:143 |
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| Enthalten in: |
European journal of medicinal chemistry - 143(2018) vom: 01. Jan., Seite 1325-1344 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Xu, Xi [VerfasserIn] |
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| Links: |
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| Themen: |
Androgen Receptor Antagonists |
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| Anmerkungen: |
Date Completed 02.01.2018 Date Revised 02.01.2018 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ejmech.2017.10.031 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM277848156 |
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| 245 | 1 | 0 | |a Exploring the tetrahydroisoquinoline thiohydantoin scaffold blockade the androgen receptor as potent anti-prostate cancer agents |
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| 500 | |a Date Revised 02.01.2018 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2017 Elsevier Masson SAS. All rights reserved. | ||
| 520 | |a Prostate cancer (PC) is a major cause of cancer-related male death in worldwide and the identification of new and improved potent anti-PC molecules is constantly required. A novel scaffold of tetrahydroisoquinoline thiohydantoin was rationally designed based on the enzalutamide structures and our pre-work, leading to the discovery of a series of new antiproliferative compounds. Several new analogues displayed improved androgen receptor (AR) antagonistic activity, while maintaining the higher selective toxicity toward LNCaP cells (AR-rich) versus DU145 cells (AR-deficient) compared to enzalutamide. In fact, compound 55 exhibited promising in vitro antitumor activity by impairing AR unclear translocation. More importantly, 55 showed better pharmacokinetic properties compared to the compound 1 reported in our pre-work. These results demonstrate a step towards the development of novel and improved AR antagonists | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Androgen receptor | |
| 650 | 4 | |a Antagonist | |
| 650 | 4 | |a Prostate cancer | |
| 650 | 4 | |a Tetrahydroisoquinoline thiohydantoin derivatives | |
| 650 | 7 | |a Androgen Receptor Antagonists |2 NLM | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a Receptors, Androgen |2 NLM | |
| 650 | 7 | |a Thiohydantoins |2 NLM | |
| 700 | 1 | |a Ge, Raoling |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jubo |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Xiaoyu |e verfasserin |4 aut | |
| 700 | 1 | |a Xue, Siqi |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Xijing |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Zhiyu |e verfasserin |4 aut | |
| 700 | 1 | |a Bian, Jinlei |e verfasserin |4 aut | |
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