Synthesis and Activity Evaluation of Nasopharyngeal Carcinoma Inhibitors Based on 6-(Pyrimidin-4-yl)-1H-indazole.
Chem Biodivers
; 16(5): e1800598, 2019 May.
Article
em En
| MEDLINE
| ID: mdl-30788913
ABSTRACT
Human nasopharyngeal carcinoma is a common head and neck malignancy with high incidence in Southeast Asia and Southern China. It is necessary to develop safe, effective and inexpensive anticancer agents to improve the therapeutics of patients with nasopharyngeal carcinoma. A series of small molecular compounds based on 6-(pyrimidin-4-yl)-1H-indazole were synthesized and evaluated for antiproliferative activities against human nasopharyngeal carcinoma cell lines SUNE1. Compounds 6b, 6c, 6e and 6l showed potent antiproliferative activities similar to positive control drug cisplatin inâ
vitro with lower nephrotoxicity than it. N-[4-(1H-Indazol-6-yl)pyrimidin-2-yl]benzene-1,3-diamine (6l) was selected for further study. It was found that 6l induced mitochondria-mediated apoptosis and G2 /M phase arrest in SUNE1 cells. Furthermore, compound 6l at 10â
mg/kg can suppress the growth of an implanted SUNE1 xenograft with a TGI% (tumor growth inhibition) value of 50 % and did not cause serious side effects in BALB/c nude mice. This study suggests that 6-(pyrimidin-4-yl)-1H-indazole derivatives are a series of small molecule compounds with anti-nasopharyngeal carcinoma activities.
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01-internacional
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Geral
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MEDLINE
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Indazóis
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Antineoplásicos
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Animals
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Humans
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En
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Chem Biodivers
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BIOQUIMICA
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QUIMICA
Ano de publicação:
2019
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Article