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Design, synthesis and bioevaluation of novel 6-substituted aminoindazole derivatives as anticancer agents
In the present study, a series of 6-substituted aminoindazole derivatives were designed, synthesized, and evaluated for bio-activities. The compounds were initially designed as indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors based on the structural feature of five IDO1 inhibitors, which are currentl...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9058813/ https://www.ncbi.nlm.nih.gov/pubmed/35516257 http://dx.doi.org/10.1039/d0ra09112j |
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author | Hoang, Ngo Xuan Hoang, Van-Hai Luu, Thi-Thu-Trang Luu, Hung N. Ngo, Thien Van Hieu, Duong Long, Nguyen Huu Anh, Le Viet Ngo, Son Tung Nguyen, Yen Thi Kim Han, Byung Woo Nguyen, Thanh Xuan Hai, Dinh Thi Thanh Hien, Tran Thi Thu Tran, Phuong-Thao |
author_facet | Hoang, Ngo Xuan Hoang, Van-Hai Luu, Thi-Thu-Trang Luu, Hung N. Ngo, Thien Van Hieu, Duong Long, Nguyen Huu Anh, Le Viet Ngo, Son Tung Nguyen, Yen Thi Kim Han, Byung Woo Nguyen, Thanh Xuan Hai, Dinh Thi Thanh Hien, Tran Thi Thu Tran, Phuong-Thao |
author_sort | Hoang, Ngo Xuan |
collection | PubMed |
description | In the present study, a series of 6-substituted aminoindazole derivatives were designed, synthesized, and evaluated for bio-activities. The compounds were initially designed as indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors based on the structural feature of five IDO1 inhibitors, which are currently on clinical trials, and the important anticancer activity of the indazole scaffold. One of them, compound N-(4-fluorobenzyl)-1,3-dimethyl-1H-indazol-6-amine (36), exhibited a potent anti-proliferative activity with an IC(50) value of 0.4 ± 0.3 μM in human colorectal cancer cells (HCT116). This compound also remarkably suppressed the IDO1 protein expression. In the cell-cycle studies, the suppressive activity of compound 36 in HCT116 cells was related to the G2/M cell cycle arrest. Altogether, the current findings demonstrate that compound 36 would be promising for further development as a potential anticancer agent. |
format | Online Article Text |
id | pubmed-9058813 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-90588132022-05-04 Design, synthesis and bioevaluation of novel 6-substituted aminoindazole derivatives as anticancer agents Hoang, Ngo Xuan Hoang, Van-Hai Luu, Thi-Thu-Trang Luu, Hung N. Ngo, Thien Van Hieu, Duong Long, Nguyen Huu Anh, Le Viet Ngo, Son Tung Nguyen, Yen Thi Kim Han, Byung Woo Nguyen, Thanh Xuan Hai, Dinh Thi Thanh Hien, Tran Thi Thu Tran, Phuong-Thao RSC Adv Chemistry In the present study, a series of 6-substituted aminoindazole derivatives were designed, synthesized, and evaluated for bio-activities. The compounds were initially designed as indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors based on the structural feature of five IDO1 inhibitors, which are currently on clinical trials, and the important anticancer activity of the indazole scaffold. One of them, compound N-(4-fluorobenzyl)-1,3-dimethyl-1H-indazol-6-amine (36), exhibited a potent anti-proliferative activity with an IC(50) value of 0.4 ± 0.3 μM in human colorectal cancer cells (HCT116). This compound also remarkably suppressed the IDO1 protein expression. In the cell-cycle studies, the suppressive activity of compound 36 in HCT116 cells was related to the G2/M cell cycle arrest. Altogether, the current findings demonstrate that compound 36 would be promising for further development as a potential anticancer agent. The Royal Society of Chemistry 2020-12-22 /pmc/articles/PMC9058813/ /pubmed/35516257 http://dx.doi.org/10.1039/d0ra09112j Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/ |
spellingShingle | Chemistry Hoang, Ngo Xuan Hoang, Van-Hai Luu, Thi-Thu-Trang Luu, Hung N. Ngo, Thien Van Hieu, Duong Long, Nguyen Huu Anh, Le Viet Ngo, Son Tung Nguyen, Yen Thi Kim Han, Byung Woo Nguyen, Thanh Xuan Hai, Dinh Thi Thanh Hien, Tran Thi Thu Tran, Phuong-Thao Design, synthesis and bioevaluation of novel 6-substituted aminoindazole derivatives as anticancer agents |
title | Design, synthesis and bioevaluation of novel 6-substituted aminoindazole derivatives as anticancer agents |
title_full | Design, synthesis and bioevaluation of novel 6-substituted aminoindazole derivatives as anticancer agents |
title_fullStr | Design, synthesis and bioevaluation of novel 6-substituted aminoindazole derivatives as anticancer agents |
title_full_unstemmed | Design, synthesis and bioevaluation of novel 6-substituted aminoindazole derivatives as anticancer agents |
title_short | Design, synthesis and bioevaluation of novel 6-substituted aminoindazole derivatives as anticancer agents |
title_sort | design, synthesis and bioevaluation of novel 6-substituted aminoindazole derivatives as anticancer agents |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9058813/ https://www.ncbi.nlm.nih.gov/pubmed/35516257 http://dx.doi.org/10.1039/d0ra09112j |
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