Advanced Search
YUSUPUWAJIMU Alimujiang, AIZITIAILI Aihaiti, MOURBOUL Ablise, YANG Zheng, SAILIKEALA Alihan, LIU Zhengye. Design, synthesis and anti-cervical cancer activity of novel trifluoromethyl chalcones derivatives[J]. Journal of China Pharmaceutical University, 2022, 53(6): 674-684. DOI: 10.11665/j.issn.1000-5048.20220605
Citation: YUSUPUWAJIMU Alimujiang, AIZITIAILI Aihaiti, MOURBOUL Ablise, YANG Zheng, SAILIKEALA Alihan, LIU Zhengye. Design, synthesis and anti-cervical cancer activity of novel trifluoromethyl chalcones derivatives[J]. Journal of China Pharmaceutical University, 2022, 53(6): 674-684. DOI: 10.11665/j.issn.1000-5048.20220605
shu

Design, synthesis and anti-cervical cancer activity of novel trifluoromethyl chalcones derivatives

  • College of Pharmacy, Xinjiang Medical University, Urumqi 830011, China

Funds: This study was supported by the National Natural Science Foundation of China (No.81960625); and the Project of Xinjiang Key Laboratory of Natural Medicine Active Components and Drug Release Technology (No.XJDX1713)
More Information
  • Received Date: October 12, 2022
  • Revised Date: November 17, 2022
    Graphical Abstract
    • Abstract
  • Chalcones are polyphenolic flavonoid substances with various pharmacological effects and low toxicity.In this study, 15 novel trifluoromethyl chalcone derivatives (3a-3o) were designed and synthesized using the chalcone nucleus of natural licorice chalcone as the lead compound skeleton in order to find the candidate drugs with high efficiency and low toxicity against cervical cancer.The structures of the target compounds were confirmed by 1H NMR, 13C NMR and HRMS. The inhibitory activities of compounds 3a-3o, licorice chalcone, cisplatin and Nutlin3a on SiHa, HeLa and C-33A human cervical cancer cells and H8 and HaCaT normal cells were determined by MTT assay, and the structure-activity relationship was analyzed.Transwell and flow cytometry methods were used to assess the target compounds' ability to inhibit cell migration and invasion, promote apoptosis, and arrest the cell cycle.Molecular docking technology was used to further study the binding characteristics of the target compound with MDM2 protein.The results showed that the compounds had different degrees of inhibitory activity against the three types of cervical cancer cells.Compound 3n showed the strongest activity against HeLa cells (IC50 = 11.69 μmol/L), which was superior to the lead compound, and had lower toxicity against the two normal cells.Compound 3n was found to significantly inhibit the migration and invasion of HeLa cells, induce apoptosis and arrest the cell cycle at G2/M phase.The results of molecular docking showed that the effective binding of compound 3n to MDM2 protein may be one of its anti-tumor mechanisms.This study provides an experimental basis for the screening of new anti-cervical cancer candidate drug from chalcone derivatives.
    • FullText(HTML)
    • References (27)
  • [1]
    . Int J Environ Res Public Health，2022，19（12）：7094.
    [2]
    di Fiore R，Suleiman S，Drago-Ferrante R，et al. Cancer stem cells and their possible implications in cervical cancer：a short review［J］. Int J Mol Sci，2022，23（9）：5167.
    [3]
    Sung H，Ferlay J，Siegel RL，et al. Global cancer statistics 2020：GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries［J］. CA Cancer J Clin，2021，71（3）：209-249.
    [4]
    Liu ZC，Li ZX，Zhang Y，et al. Interpretation on the report of global cancer statistics 2020［J］. J Multidiscip Cancer Manag Electronic Version（肿瘤综合治疗电子杂志），2021，7（2）：1-14.
    [5]
    Dre?canu G，Iuhas CI，Diaconeasa Z. The involvement of natural polyphenols in the chemoprevention of cervical cancer［J］. Int J Mol Sci，2021，22（16）：8812.
    [6]
    He MZ，Xia LJ，Li JY. Potential mechanisms of plant-derived natural products in the treatment of cervical cancer［J］. Biomolecules，2021，11（10）：1539.
    [7]
    He XL，Liao YK，Liu J，et al. Research progress of natural small-molecule compounds related to tumor differentiation［J］. Molecules，2022，27（7）：2128.
    [8]
    Xiong JF，Li GN，Mei XY，et al. Co-delivery of p53 restored and E7 targeted nucleic acids by poly（beta-amino ester） complex nanoparticles for the treatment of HPV related cervical lesions［J］. Front Pharmacol，2022，13：826771.
    [9]
    Kooti A，Abuei H，Farhadi A，et al. Activating transcription factor 3 mediates apoptotic functions through a p53-independent pathway in human papillomavirus 18 infected HeLa cells［J］. Virus Genes，2022，58（2）：88-97.
    [10]
    Heijkants RC，Teunisse AFAS，de Jong D，et al. MDMX regulates transcriptional activity of p53 and FOXO proteins to stimulate proliferation of melanoma cells［J］. Cancers（Basel），2022，14（18）：4482.
    [11]
    Chinnam M，Xu C，Lama R，et al. MDM2 E3 ligase activity is essential for p53 regulation and cell cycle integrity［J］. PLoS Genet，2022，18（5）：e1010171.
    [12]
    Zhang JW，Yu GH，Yang YT，et al. A small-molecule inhibitor of MDMX suppresses cervical cancer cells via the inhibition of E6-E6AP-p53 axis［J］. Pharmacol Res，2022，177：106128.
    [13]
    Espadinha M，Lopes EA，Marques V，et al. Discovery of MDM2-p53 and MDM4-p53 protein-protein interactions small molecule dual inhibitors［J］. Eur J Med Chem，2022，241：114637.
    [14]
    Grinkevich VV，Vema A，Fawkner K，et al. Novel allosteric mechanism of dual p53/MDM2 and p53/MDM4 inhibition by a small molecule［J］. Front Mol Biosci，2022，9：823195.
    [15]
    de Souza PS，Bibá GCC，Melo EDDN，et al. Chalcones against the hallmarks of cancer：a mini-review［J］. Nat Prod Res，2022，36（18）：4809-4826.
    [16]
    Constantinescu T，Lungu CN. Anticancer activity of natural and synthetic chalcones［J］. Int J Mol Sci，2021，22（21）：11306.
    [17]
    Shukla S，Sood AK，Goyal K，et al. Chalcone scaffolds as anticancer drugs：a review on molecular insight in action of mechanisms and anticancer properties［J］. Anticancer Agents Med Chem，2021，21（13）：1650-1670.
    [18]
    Ouyang Y，Li JJ，Chen XY，et al. Chalcone derivatives：role in anticancer therapy［J］. Biomolecules，2021，11（6）：894.
    [19]
    Wang JC，Yang CB，Zhuo YL，et al. Recent advances of MDM2-p53 inhibitors［J］. Acta Pharm Sin（药学学报），2021，56（4）：983-995.
    [20]
    Si DJ，Luo HJ，Zhang XM，et al. Design，synthesis and biological evaluation of novel pyrrolidone-based derivatives as potent p53-MDM2 inhibitors［J］. Bioorg Chem，2021，115：105268.
    [21]
    Mireguli M. Preparation and anti-cervical cancer activity of glycyrrhiza inflata chalcones and its derivatives（胀果甘草查耳酮类活性成分及其衍生物的制备及抗宫颈癌活性研究）［D］. Xinjiang：Xinjiang Medical University，2020.
    [22]
    Liu LM，Wang ZJ，Gao C，et al. Design，synthesis and antitumor activity evaluation of trifluoromethyl-substituted pyrimidine derivatives［J］. Bioorg Med Chem Lett，2021，51：128268.
    [23]
    Wang ZJ，Dai HL，Si XJ，et al. Synthesis and antitumor activity of 2，4，6-trisubstituted novel quinazoline derivatives containing trifluoromethyl［J］. Chin J Org Chem（有机化学），2022，42（1）：249-256.
    [24]
    Aizitiaili A，Yang Z，Mourboul A，et al. Synthesis and anti-cervical cancer activities of novel α-methyl chalcone derivatives［J］. Chin J Med Chem（中国药物化学杂志），2022，32（1）：8-18.
    [25]
    Yuan H，Zuo J，Li N，et al. Fronter research on drug treatment of gynecological oncology［J］. Chin J Cancer Prevention and Treatment（中华肿瘤防治杂志），2022，29（14）：1023-1032.
    [26]
    Islam F，Mitra S，Emran TB，et al. Natural small molecules in gastrointestinal tract and associated cancers：molecular insights and targeted therapies［J］. Molecules，2022，27（17）：5686.
    [27]
    Sun TZ. Mathematical modeling of the synergy between hyperthermia and radiotherapy in tumor treatment based on p53 signaling network［J］. J China Pharm Univ（中国药科大学学报），2021，52（3）：361-370.
    • Related Articles

  • Related Articles

    [1]CAI Yanfei, WAN Aini, CHEN Yun, JIN Jian. Anti-liver fibrosis activities of the extracellular domain of transforming growth factor beta type II receptor fusion protein in vivo[J]. Journal of China Pharmaceutical University, 2019, 50(2): 246-252. DOI: 10.11665/j.issn.1000-5048.20190217
    [2]WAN Aini, XU Dongsheng, CAI Yanfei, CHEN Yun, JIN Jian, LI Huazhong. Anti-liver fibrosis activities of human insulin-like growth factor-1 in vitro[J]. Journal of China Pharmaceutical University, 2017, 48(4): 476-482. DOI: 10.11665/j.issn.1000-5048.20170413
    [3]Expression and Activity Identification of Shortened Human Acidic Fibroblast Growth Factor[J]. Journal of China Pharmaceutical University, 2004, (5): 84-87.
    [4]Effective Expression and Purification of Human Insulin Like Growth Factor-1 in Bombyx Mori Nuclear Polyhedrosis Virus System[J]. Journal of China Pharmaceutical University, 2004, (2): 76-80.
    [5]Effect of Lovastatin on the Expression of Insulin-like Growth Factor-1 in the Cultured Human Mesangial Cells[J]. Journal of China Pharmaceutical University, 2003, (6): 43-47.
    [6]The Status of Fibroblast Growth Factor Use in the Treatment of Coronary Heart Disease Research[J]. Journal of China Pharmaceutical University, 2003, (3): 89-94.
    [7]Expression of Human Transforming Growth Factor β3 in E.coli BL21[J]. Journal of China Pharmaceutical University, 2003, (3): 70-73.
    [8]Influence of Irbesartan on the Expression of Connective Tissue Growth Factor in Streptozotocin Induced Diabetic Rats[J]. Journal of China Pharmaceutical University, 2002, (4): 64-68.
    [9]Study of Recombinant Human Acidic Fibroblast Growth Factor on Improving Wound Healing in Rabbits[J]. Journal of China Pharmaceutical University, 2002, (4): 50-53.

Catalog

    Get Citation
    PDF
    XML
    Article views PDF downloads Cited by()
    Turn off MathJax
    Article Contents
    Abstract
    References
    Related Articles

    Copyright © Journal of China Pharmaceutical University苏ICP备12050101号-2

    Address：24 Tongjia Lane, Nanjing City, Jiangsu Province （210009）Tel: 025-83271566E-mail: xuebao@cpu.edu.cn

    Supported by: Beijing Renhe Information Technology Co., Ltd.  Baidu Analytics

    Total visits：436420

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return