Takács Angéla, Jessen Malin, Lajkó Eszter, Szász Zsófia, Kalabay Márton, Csámpai Antal, Kőhidai László
Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.
Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary; Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
Biomed Pharmacother. 2025 Jun;187:118076. doi: 10.1016/j.biopha.2025.118076. Epub 2025 Apr 22.
Chincona alkaloids extracted from the bark stem of Cinchona officinalis have been historically used to treat fever and malaria. More recently, cinchona alkaloid derivatives have been attributed to apoptotic effects in the context of cancer. Similarly, chalcones are plant-derived polyphenolic compounds with known anti-fungal, -microbial, -malarial, and -carcinogenic properties. Here, we reveal cytotoxic and antiproliferative characteristics of synthetic quinine-chalcone hybrids in human cancer cell lines. Two derivatives (AD-12 and AD-13) presented IC values below 2 µM in the lung squamous cell carcinoma cell line (EBC-1). Our study shows that AD-12 and AD-13 increased intracellular ROS levels and promoted caspase-3/7, and -8 activity in EBC-1 cells. These apoptotic effects were accompanied by short-term inhibition of P-gp efflux activity, while expression levels of P-gp transporters remained stable. Together, our study illustrates the potential of quinine-chalcone hybrids as novel anticancer drug candidates.
从金鸡纳树的树皮茎中提取的金鸡纳生物碱在历史上一直被用于治疗发烧和疟疾。最近，金鸡纳生物碱衍生物在癌症背景下具有凋亡作用。同样，查耳酮是植物来源的多酚化合物，具有已知的抗真菌、抗微生物、抗疟疾和致癌特性。在这里，我们揭示了合成奎宁-查耳酮杂化物在人癌细胞系中的细胞毒性和抗增殖特性。两种衍生物（AD-12和AD-13）在肺鳞状细胞癌细胞系（EBC-1）中的IC值低于2μM。我们的研究表明，AD-12和AD-13增加了EBC-1细胞内的活性氧水平，并促进了caspase-3/7和-8的活性。这些凋亡作用伴随着P-糖蛋白外排活性的短期抑制，而P-糖蛋白转运体的表达水平保持稳定。总之，我们的研究说明了奎宁-查耳酮杂化物作为新型抗癌药物候选物的潜力。
