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

YUSUPUWAJIMU Alimujiang; AIZITIAILI Aihaiti; MOURBOUL Ablise; YANG Zheng; SAILIKEALA Alihan; LIU Zhengye

doi:10.11665/j.issn.1000-5048.20220605

Journal of China Pharmaceutical University > 2022 > 53(6): 674-684. > DOI: 10.11665/j.issn.1000-5048.20220605

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

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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)

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Received Date: October 12, 2022
Revised Date: November 17, 2022

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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.
- chalcone derivatives,
- synthesis,
- cervical cancer,
- proliferation inhibition,
- apoptosis,
- anti-tumor activity

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