School of Pharmacy, Xiamen Medical College, Xiamen 361023, China.
Xiamen Medical College Research Center for Sustained and Controlled Release Formulations, Xiamen Medical College, Xiamen 361023, China.
Molecules. 2024 Jun 25;29(13):3010. doi: 10.3390/molecules29133010.
Cancer is one of the deadliest diseases to humanity. There is significant progress in treating this disease, but developing some drugs that can fight this disease remains a challenge in the field of medical research. Thirteen new 1,2,3-triazole linked tetrahydrocurcumin derivatives were synthesized by click reaction, including a 1,3-dipolar cycloaddition reaction of tetrahydrocurcumin baring mono-alkyne with azides in good yields, and their in vitro anticancer activity against four cancer cell lines, including human cervical carcinoma (HeLa), human lung adenocarcinoma (A549), human hepatoma carcinoma (HepG2), and human colon carcinoma (HCT-116) were investigated using MTT(3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetraz-olium bromide) assay. The newly synthesized compounds had their structures identified using NMR HRMS and IR techniques. Some of prepared compounds, including compounds and , showed potent cytotoxic activity against four cancer cell lines compared to the positive control of cisplatin and tetrahydrocurcumin. Compound exhibited anticancer activity with a IC value of 1.09 ± 0.17 μM against human colon carcinoma HCT-116 and 45.16 ± 0.92 μM against A549 cell lines compared to the positive controls of tetrahydrocurcumin and cisplatin. Moreover, further biological examination in HCT-116 cells showed that compound can arrest the cell cycle at the G1 phase. A docking study revealed that the potential mechanism by which exerts its anti-colon cancer effect may be through inhabiting the binding of APC-Asef. Compound can be used as a promising lead for further exploration of potential anticancer agents.
癌症是对人类最致命的疾病之一。在治疗这种疾病方面已经取得了重大进展，但开发能够对抗这种疾病的药物仍然是医学研究领域的一个挑战。通过点击反应合成了 13 种新的 1,2,3-三唑连接的四氢姜黄素衍生物，包括四氢姜黄素单炔基与叠氮化物的 1,3-偶极环加成反应，以良好的产率得到，并用 MTT（3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四唑溴盐）测定法研究了它们对四种癌细胞系（人宫颈癌（HeLa）、人肺腺癌（A549）、人肝癌（HepG2）和人结肠癌细胞（HCT-116）的体外抗癌活性。新合成的化合物通过 NMR HRMS 和 IR 技术确定了其结构。一些合成的化合物，包括化合物和，与顺铂和四氢姜黄素的阳性对照相比，对四种癌细胞系表现出更强的细胞毒性活性。与阳性对照物四氢姜黄素和顺铂相比，化合物在人结肠癌细胞 HCT-116 中的抗癌活性的 IC 值为 1.09 ± 0.17 μM，在 A549 细胞系中的抗癌活性的 IC 值为 45.16 ± 0.92 μM。此外，在 HCT-116 细胞中的进一步生物学研究表明，化合物可以将细胞周期阻滞在 G1 期。对接研究表明，化合物发挥其抗结肠癌作用的潜在机制可能是通过抑制 APC-Asef 的结合。化合物可作为进一步探索潜在抗癌药物的有前途的先导化合物。
