- Novel CDKs inhibitors for the treatment of solid tumour by simultaneously regulating the cell cycle and transcription control
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A novel series of cyclin-dependent kinases (CDKs) inhibitors, which play critical roles in the cell cycle control and regulation of cell transcription, were synthesised. A systematic study of enzymatic and cellular assays led to the identification of compound X22 with a nanomolar potency against CDK4 and CDK9 and potent antiproliferative activities against a panel of tumour cell lines. X22 could induce cell cycle arrest and cell apoptosis in cancer cell lines. X22 dose-dependently inhibits signalling pathways downstream of CDKs in cancer cells. In vivo antitumor activity assays, oral administration of X22 led to significant tumour regression in mouse model without obvious toxicity. Superior anti-cancer efficacy in vitro and in vivo of X22 demonstrated combined depletion of cell cycle and transcriptional CDK all contributed to antitumor activity. Taken together, concomitant inhibition of cell cycle and transcriptional CDK activities provided valuable guide for further structural optimisation.
- Deng, Kaiyuan,Fan, Yan,Huang, Zhi,Li, Yao,Ma, Yakun,Shi, Yi,Sun, Peiqing,Wang, Cheng,Wang, Tianqi,Wang, Xin,Xiang, Rong,Yang, Shengyong
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- Synthesis and evaluation of novel erucin analogues as potential antitumor compounds
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Background:Several studies have shown excellent antitumor activity of erucin, but there are few studies on its analogues. The aim of the study involves the synthesis and the antitumor activities of novel erucin analogues. Ten novel erucin analogues were synthesized and evaluated for their efficacy as antitumor agents. Methods: Ten novel erucin analogues were synthesized by using 1, 4-dibromobutane and potassium phthalimide as starting materials, and the antitumor activities in vitro was screened against breast cancer cells (MCF-7), cervical cancer cells (HeLa-229) and lung cancer cells (A549). Results: The structures of these novel compounds were confirmed by1H NMR,13C NMR and elemental analysis. The preliminary bioassay results demonstrated that all of the tested compounds showed potent antitumor activities. Among these compounds, compound 6b showed the best inhibitory effect against MCF-7 with IC50 value of 0.46 μM and A549 with IC50 value of 0.44 μM. Compound 6f also displayed the best inhibitory effect against HeLa-229 with IC50 value of 0.32 μM. Conclusion: Synthesis and screening of antitumor activities were performed for a novel series of erucin analogues. All of the synthetic compounds showed potent antitumor activities against breast cancer cells (MCF-7), cervical cancer cells (HeLa-229) and lung cancer cells (A549). Compounds 6b and 6f were found to be the most active against most of the tested cancer cells.
- Shao, Yan-Dong,Song, Huang-Wang,Feng, Wen,Wang, Xiang-Hui,Shi, Zai-Feng,Wu, Lu-Yong,Chen, Guang-Ying,Lin, Qiang
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p. 206 - 213
(2018/03/09)
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- Thioether allyl isothiocyanate compounds, and preparation method and applications thereof
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The invention provides a series of novel thioether allyl isothiocyanate compounds with a general structure disclosed in the invention, and a simple method used for rapid synthesis of the thioether allyl isothiocyanate compounds. According to the method, double-terminal halogen-substituted alkanes are taken as initial raw materials, are reacted with phthalimide potassium so as to introduce N atoms, are reacted with sodium hydrosulfide so as to produce mercaptan, and mercaptan is reacted with benzyl bromide or is reacted with a heterocyclic compound with sulfydryl so as to introduce the thioether structure, an obtained product is reacted with hydrazine hydrate so as to obtain a primary amine, and the primary amine is reacted with an alkali, carbon disulfide, and methylsufonyl chloride so as to prepare the thioether allyl isothiocyanate compounds with heterocyclic nitrogen structures. The method contains few steps; operation is simple; the obtained products can be easily purified; and yield is high. The series of novel thioether allyl isothiocyanate compounds possess obvious killing activity on tumor cells, and possess obvious killing activity on cervical carcinoma cells and lung cancer cells.
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Paragraph 0051; 0066; 0067; 0068; 0077
(2016/10/08)
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- Synthesis and biological evaluation of sulforaphane derivatives as potential antitumor agents
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A series of sulforaphane derivatives were synthesized and evaluated in vitro for their cytotoxicity against five cancer cell lines (HepG2, A549, MCF-7, HCT-116 and SH-SY5Y). The pharmacological results showed that many of the derivatives displayed more potent cytotoxicity than sulforaphane (SFN). Furthermore, SFN and derivative 85 could induce cell cycle arrest at S or G2/M phase and cell apoptosis. SFN and 85 exhibited time- and dose-dependent activation on Nrf2 transcription factor, and 85 acted as a more potent Nrf2 inducer than SFN.
- Hu, Kun,Qi, Yan-Jie,Zhao, Juan,Jiang, He-Fei,Chen, Xin,Ren, Jie
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p. 529 - 539
(2013/07/11)
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