Department of Chemistry, Faculty of Science and Technology, Rambhai Barni Rajabhat University, Chanthaburi 22000, Thailand.
Department of Chemistry and Center for Innovation in Chemistry, Faculty of Science, Burapha University, Chonburi 20131, Thailand.
Bioorg Med Chem. 2021 Jan 1;29:115886. doi: 10.1016/j.bmc.2020.115886. Epub 2020 Dec 1.
A novel series of acanthoic acid analogues containing triazole moiety were synthesized through esterification and CuAAC reaction. Evaluation of their biological activities against four cell lines of cholangiocarcinoma cells showed that 3d exhibited the strongest activity with an IC value of 18 µM against KKU-213 cell line, which was 8 fold more potent than acanthoic acid. Interestingly, the triazole ring and nitro group on benzyl ring play very significant role in cytotoxic activity. The computational studies revealed that 3d occupies the binding energy of -12.7 and -10.8 kcal/mol with CDK-2 and EGFR protein kinases, respectively. This result might provide a beginning for the development of acanthoic acid analogues as an anticancer agent.
通过酯化和 CuAAC 反应，合成了一系列含有三唑部分的新型棘白菌素类似物。对它们对胆管癌细胞的四种细胞系的生物活性评估表明，3d 对 KKU-213 细胞系表现出最强的活性，IC 值为 18µM，比棘白菌素强 8 倍。有趣的是，三唑环和苄基环上的硝基在细胞毒性活性中起着非常重要的作用。计算研究表明，3d 分别与 CDK-2 和 EGFR 蛋白激酶的结合能为-12.7 和-10.8 kcal/mol。这一结果可能为开发棘白菌素类似物作为抗癌剂提供了一个开端。
