13338-63-1Relevant articles and documents
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Cason,J.,Lynch,D.M.
, p. 1883 - 1887 (1966)
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Combretastatin A4 analogue containing cyanoethylene joining chain and application in preparing antitumor drugs
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, (2019/03/15)
The invention a Combretastatin A4 analogue containing a cyanoethylene joining chain and an application in preparing antitumor drugs, which relates to the field of a medicinal compound. A structural formula (I-IV) is shown as the specification, an anticancer candidate compound which has strong inhibitory activity against cancer cells and is not toxic to normal cells is currently lacked, for the reason, the method prepares 19 I-IV series compounds, and the para and meta positions of the B ring (benzene ring) introduce various alkyl groups, alkoxy groups or amino substituents or replace the B ring (benzene ring) with various heterocyclic rings. In the I-series compound, when the para position of the B ring (benzene ring) is substituted with an ethyl group, an isopropyl group, a dimethylaminogroup or a diethylamino group, the proliferation resistance of the cancer cells is very strong, and toxicity is weak for the L-02 normal cells, a selective anticancer activity coefficient (an IC50 value ratio of L-02 normal cells to cancer cells) can even exceed 10,000, and the four compounds have the potential to be developed into safe and highly effective anticancer drugs.
Synthesis and characterisation of (Z)-styrylbenzene derivatives as potential selective anticancer agents
Xin, Ya-Bing,Li, Jia-Jun,Zhang, Hong-Jian,Ma, Jun,Liu, Xin,Gong, Guo-Hua,Tian, Yu-Shun
, p. 1554 - 1564 (2018/10/02)
To identify anticancer agents with high potency and low toxicity, a series of (Z)-styrylbenzene derivatives were synthesised and evaluated for anticancer activities using a panel of nine cancer cell lines and two noncancerous cell lines. Most derivatives exhibited significant anti-proliferative activities against five cancer cell lines, including MGC-803 and BEL-7402. (Z)-3-(p-Tolyl)-2-(3,4,5-trimethoxyphenyl)acrylonitrile (6h) showed a strong inhibitory effect on MGC-803 cells (IC50 50 50 value of 6h in L-02 cells was 10,000-fold higher than in MGC-803 cells. Compound 6h inhibited proliferation of BEL-7402 cells by arresting at the G2/M phase through up-regulation of cyclin B1 expression, down-regulation of cyclin A and D1 expression, and induction of apoptosis. In addition, 6h inhibited the migration of BEL-7402 cells and the formation of cell colonies.
Anti-acute myeloid leukemia activity of 2-chloro-3-alkyl-1,4-naphthoquinone derivatives through inducing mtDNA damage and GSH depletion
Li, Kun,Yang, Kun,Zheng, Lifang,Li, Yuanyuan,Wang, Qi,Lin, Ruili,He, Dian
, p. 4191 - 4200 (2018/07/21)
2-Chloro-3-alkyl-1,4-naphthoquinone derivatives were synthesized and tested as the anti-acute myeloid leukaemia agents. The compound 9b (2-chloro-3-ethyl-5,6,7-trimethoxy-1,4-naphthoquinone) was the most potent toward HL-60 leukaemia cells. In mechanistic study for 9b, the protein levels of mtDNA-specific DNA polymerase γ (poly-γ) and mtDNA transcription factor A (mt-TFA) were decreased after the 24 h treatment, showing the occurrence of mtDNA damage. And 9b triggered cell cycle arrest at S phase accompanied by a secondary block in G2/M phase which had a direct link to the process of mtDNA damage. The dissipations of mitochondrial membrane potential and ATP also proceeded. On the other hand, 9b promoted the generation of ROS and resulted in the oxidation of intracellular GSH to GSSG. This process was coupled to the formation of adduct between 9b and GSH, detected by the UV–Vis spectrum and HRMS analysis. Depletion of GSH by buthionine sulfoximine enhanced ROS level and produced higher cytotoxicity, suggesting GSH was involved in the anti-leukemic mechanism of 9b. Together, our results provide new insights on the molecular mechanism of the derivatives of 2-chloro-1,4-naphthoquinone and 9b might be useful for the further development into an anti-leukemia agent.