Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Department of Medicinal Chemistry, School of Pharmacy, Chongqing Medical University, Chongqing 400016, China.
J Med Chem. 2021 Jan 28;64(2):1018-1036. doi: 10.1021/acs.jmedchem.0c01512. Epub 2021 Jan 10.
Tetrazanbigen () is a novel sterol isoquinoline derivative with poor water solubility and moderate inhibitory effects on human cancer cell lines lipoapoptosis induction. Herein, we developed a series of novel analogues with improved water solubility and antiproliferative activities. The CCK-8 assay enabled us to identify a novel compound, , which strongly inhibited HepG2 and A549 cell growth with IC values of 0.54 and 0.47 μM, respectively. The anticancer effects might be explained by the partial activation and upregulation of PPARγ expression, as indicated by the transactivation assay and western blotting evaluation. Furthermore, the antiproliferative activity was verified in an xenograft model in which strongly reduced tumor growth at a dose of 10 mg/kg. In line with these positive observations, exhibited an excellent water solubility of 31.4 mg/mL, which was more than 1000-fold higher than that of (4 μg/mL). Together, these results suggest that is a promising anticancer therapeutic that deserves further investigation.
四氮杂苯并菲（）是一种新型甾体异喹啉衍生物，具有较差的水溶性和适度的抑制人癌细胞系增殖和诱导脂凋亡的作用。在此，我们开发了一系列水溶性和抗肿瘤活性得到改善的新型类似物。CCK-8 法检测发现一种新型化合物，对 HepG2 和 A549 细胞的生长具有较强的抑制作用，IC值分别为 0.54 和 0.47 μM。部分激活和上调 PPARγ表达可能解释了其抗癌作用，转激活测定和 Western blot 评价证实了这一点。此外，在 10 mg/kg 剂量的荷瘤模型中，也验证了 的抗肿瘤增殖活性。与这些积极的观察结果一致，具有 31.4 mg/mL 的优异水溶性，比 （4 μg/mL）高 1000 多倍。总之，这些结果表明，是一种很有前途的抗癌治疗药物，值得进一步研究。
