Jihad Marwan Imad, Mahdi Monther Faisal
Department of Pharmaceutical Chemistry, College of Pharmacy, University of Mustansiriyah, Baghdad, Iraq.
J Adv Pharm Technol Res. 2023 Jul-Sep;14(3):274-279. doi: 10.4103/JAPTR.JAPTR_282_23. Epub 2023 Jul 28.
Cancer is a disease triggered by an uncontrolled proliferation of a cluster of cells, typically originating from a single cell. Sorafenib, a widely utilized pharmaceutical, has limitations in clinical use due to pharmacokinetic challenges and the development of resistance mechanisms. This investigation aimed to synthesize new sorafenib analogs and evaluated their activity against HepG2 cell lines, specifically targeting hepatocellular carcinoma (HCC). Seven sorafenib analogs were synthesized and identified by Fourier-transform infrared spectroscopy and 1H-NMR spectra. Cytotoxicity of the analogs was assessed on the human HepG2 cancer cell line by (3-(4, 5-dimethylthazolk-2-yl)-2, 5-diphenyl tetrazolium bromide) colorimetric assay. Results revealed that among the studied compounds, 4b exhibited the most pronounced cytotoxicity against cancer cells, surpassing even the efficacy of sorafenib. This suggested that small substitutions on the NH moiety play a crucial role in the activity against the human HepG2 liver cancer cell line. These findings provide valuable insights for the development of potential anticancer-targeting HCC.
癌症是一种由一群细胞不受控制地增殖引发的疾病,通常起源于单个细胞。索拉非尼是一种广泛使用的药物,由于药代动力学方面的挑战以及耐药机制的出现,其在临床应用中存在局限性。本研究旨在合成新的索拉非尼类似物,并评估它们对肝癌细胞系HepG2的活性,该细胞系专门针对肝细胞癌(HCC)。合成了七种索拉非尼类似物,并通过傅里叶变换红外光谱和1H-NMR光谱进行了鉴定。通过(3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四氮唑)比色法评估了这些类似物对人HepG2癌细胞系的细胞毒性。结果显示,在所研究的化合物中,4b对癌细胞表现出最显著的细胞毒性,甚至超过了索拉非尼的疗效。这表明NH部分的小取代在抗人HepG2肝癌细胞系活性中起着关键作用。这些发现为开发潜在的靶向肝癌的抗癌药物提供了有价值的见解。