作为体外和体内潜在抗肿瘤剂的口香碱样衍生物的设计、半合成和生物评价。
Design, semi-synthesis and bioevaluation of koumine-like derivatives as potential antitumor agents in vitro and in vivo.
发表日期：2024
作者：
Xingjun Xu, Yan Yu, Zhiwei Wang, Han Zhou, Ling Zhang, Hao Wang, Dian Liu, Yanfang Liu, Jixia Wang, Yaopeng Zhao, Xinmiao Liang
来源：
Cell Death & Disease
摘要：
目的：设计、半合成五个系列的新型口红素样化合物，并系统评价其抗肿瘤活性。方法：评价所有化合物对四种人类癌细胞系（包括 HT-29、HCT-116、HCT-1）的抗增殖活性。 15 和 Caco-2。结果：大多数化合物表现出比 koumine 高得多的抗增殖活性 (IC50 <10 μM)。两种选定的化合物 A4 和 C5 在体内表现出与 5-FU 相当的抗肿瘤作用，以及更好的安全性。进一步的研究表明，A4和C5可以将HT-29细胞周期阻滞在G2期，提高活性氧水平，从而诱导与Erk MAPK和NF-κB信号通路抑制相关的细胞凋亡。结论：这些结果将极大地促进成药性研究这些类似 koumine 的化合物。
Aims: Five series of novel koumine-like compounds were designed, semi-synthesized and systematically evaluated for antitumor activities.Methods: All compounds were evaluated for antiproliferative activity against four human cancer cell lines, including HT-29, HCT-116, HCT-15 and Caco-2.Results: Most compounds exhibited much higher antiproliferation activities (IC50 <10 μM) than koumine. Two selected compounds A4 and C5 showed comparable antitumor effects to 5-FU in vivo, as well as better safety profiles. Further studies suggested that A4 and C5 could arrest HT-29 cell cycle in G2 phase and raise reactive oxygen species level, thus inducing cell apoptosis related to Erk MAPK and NF-κB signaling pathways inhibition.Conclusion: These results will greatly promote the druggability study of these koumine-like compounds.