Xu Weijie, Pan Ying, Wang Hong, Li Haiyan, Peng Qing, Wei Duncan, Chen Cheng, Zheng Jinhong
Department of Chemistry, Shantou University Medical College, Shantou 515041, Guangdong, China.
Department of Pharmacology, Shantou University Medical College, Shantou 515041, Guangdong, China.
Molecules. 2017 Mar 16;22(3):467. doi: 10.3390/molecules22030467.
Cancer is a major public health concern worldwide. Adverse effects of cancer treatments still compromise patients' quality of life. To identify new potential anticancer agents, a series of novel pyrazoline derivatives were synthesized and evaluated for cytotoxic effects on HepG-2 (human liver hepatocellular carcinoma cell line) and primary hepatocytes. Compound structures were confirmed by ¹H-NMR, mass spectrometry, and infrared imaging. An in vitro assay demonstrated that several compounds exerted cytotoxicity in the micromolar range. Benzo[]thiophen-2-yl-[5-(4-hydroxy-3,5-dimethoxy-phenyl)-3-(2-hydroxy-phenyl)-4,5-dihydo-pyrazol-1-yl]-methanone () was the most effective anticancer agent against HepG-2 cells owing to its notable inhibitory effect on HepG-2 with an IC value of 3.57 µM when compared with cisplatin (IC = 8.45 µM) and low cytotoxicity against primary hepatocytes. Cell cycle analysis and apoptosis/necrosis evaluation using this compound revealed that notably arrested HepG-2 cells in the G₂/M phase and induced HepG-2 cells apoptosis. Our findings indicate that compound may be a promising anticancer drug candidate.
癌症是全球主要的公共卫生问题。癌症治疗的副作用仍然会影响患者的生活质量。为了确定新的潜在抗癌药物，合成了一系列新型吡唑啉衍生物，并评估了它们对HepG-2（人肝癌细胞系）和原代肝细胞的细胞毒性作用。通过¹H-NMR、质谱和红外成像确认了化合物结构。体外试验表明，几种化合物在微摩尔范围内具有细胞毒性。苯并[]噻吩-2-基-[5-(4-羟基-3,5-二甲氧基苯基)-3-(2-羟基苯基)-4,5-二氢吡唑-1-基]-甲酮（）是针对HepG-2细胞最有效的抗癌药物，因为它对HepG-2具有显著的抑制作用，IC值为3.57 µM，与顺铂（IC = 8.45 µM）相比，对原代肝细胞的细胞毒性较低。使用该化合物进行的细胞周期分析和凋亡/坏死评估显示，显著使HepG-2细胞停滞在G₂/M期并诱导HepG-2细胞凋亡。我们的研究结果表明，化合物可能是一种有前景的抗癌药物候选物。
