Synthesis, bioactivity, and molecular docking of novel arylpiperazine derivatives as potential AR antagonists
Prostate cancer is one of the malignant tumors and the second most common malignant tumor in men. Clinically used androgen receptor (AR)–targeted drugs can antagonize androgen and inhibit tumor growth, but these drugs can cause serious resistance problems. To develop novel AR antagonists, 22 kinds o...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2022.947065/full |
| _version_ | 1828437678397325312 |
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| author | Yueheng Qi Yueheng Qi Hong Chen Shijin Chen Jianliang Shen Jingguo Li |
| author_facet | Yueheng Qi Yueheng Qi Hong Chen Shijin Chen Jianliang Shen Jingguo Li |
| author_sort | Yueheng Qi |
| collection | DOAJ |
| description | Prostate cancer is one of the malignant tumors and the second most common malignant tumor in men. Clinically used androgen receptor (AR)–targeted drugs can antagonize androgen and inhibit tumor growth, but these drugs can cause serious resistance problems. To develop novel AR antagonists, 22 kinds of arylpiperazine derivatives were designed and synthesized, and the derivatives 5, 8, 12, 19, 21, 22, 25, and 26 not only showed strong antagonistic potency (>55% inhibition) and binding affinities (IC50 <3 μM) to AR, but also showed stronger inhibitory activity to LNCaP cells versus PC-3 cells. Among them, derivative 21 exhibited the highest binding affinity for AR (IC50 = 0.65 μM) and the highest antagonistic potency (76.2% inhibition). Docking studies suggested that the derivative 21 is primarily bound to the AR-LBP site by the hydrophobic interactions. Overall, those results provided experimental methods for developing novel arylpiperazine derivatives as potent AR antagonists. |
| first_indexed | 2024-12-10T19:49:51Z |
| format | Article |
| id | doaj.art-da680580f01341b6a294f1ebb1650049 |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-12-10T19:49:51Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-da680580f01341b6a294f1ebb16500492022-12-22T01:35:48ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462022-08-011010.3389/fchem.2022.947065947065Synthesis, bioactivity, and molecular docking of novel arylpiperazine derivatives as potential AR antagonistsYueheng Qi0Yueheng Qi1Hong Chen2Shijin Chen3Jianliang Shen4Jingguo Li5Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaLuoyang Key Laboratory of Organic Functional Molecules, College of Food and Drug, Luoyang Normal University, Luoyang, Henan, ChinaLuoyang Key Laboratory of Organic Functional Molecules, College of Food and Drug, Luoyang Normal University, Luoyang, Henan, ChinaLuoyang Key Laboratory of Organic Functional Molecules, College of Food and Drug, Luoyang Normal University, Luoyang, Henan, ChinaSchool of Ophthalmology & Optometry, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang, ChinaHenan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaProstate cancer is one of the malignant tumors and the second most common malignant tumor in men. Clinically used androgen receptor (AR)–targeted drugs can antagonize androgen and inhibit tumor growth, but these drugs can cause serious resistance problems. To develop novel AR antagonists, 22 kinds of arylpiperazine derivatives were designed and synthesized, and the derivatives 5, 8, 12, 19, 21, 22, 25, and 26 not only showed strong antagonistic potency (>55% inhibition) and binding affinities (IC50 <3 μM) to AR, but also showed stronger inhibitory activity to LNCaP cells versus PC-3 cells. Among them, derivative 21 exhibited the highest binding affinity for AR (IC50 = 0.65 μM) and the highest antagonistic potency (76.2% inhibition). Docking studies suggested that the derivative 21 is primarily bound to the AR-LBP site by the hydrophobic interactions. Overall, those results provided experimental methods for developing novel arylpiperazine derivatives as potent AR antagonists.https://www.frontiersin.org/articles/10.3389/fchem.2022.947065/fullprostate cancersynthesisantagonistic activitybinding affinitiesmolecular docking |
| spellingShingle | Yueheng Qi Yueheng Qi Hong Chen Shijin Chen Jianliang Shen Jingguo Li Synthesis, bioactivity, and molecular docking of novel arylpiperazine derivatives as potential AR antagonists Frontiers in Chemistry prostate cancer synthesis antagonistic activity binding affinities molecular docking |
| title | Synthesis, bioactivity, and molecular docking of novel arylpiperazine derivatives as potential AR antagonists |
| title_full | Synthesis, bioactivity, and molecular docking of novel arylpiperazine derivatives as potential AR antagonists |
| title_fullStr | Synthesis, bioactivity, and molecular docking of novel arylpiperazine derivatives as potential AR antagonists |
| title_full_unstemmed | Synthesis, bioactivity, and molecular docking of novel arylpiperazine derivatives as potential AR antagonists |
| title_short | Synthesis, bioactivity, and molecular docking of novel arylpiperazine derivatives as potential AR antagonists |
| title_sort | synthesis bioactivity and molecular docking of novel arylpiperazine derivatives as potential ar antagonists |
| topic | prostate cancer synthesis antagonistic activity binding affinities molecular docking |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2022.947065/full |
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