School of Biological Science and Technology, University of Jinan, Jinan, Shandong Province 250022, China.
School of Biological Science and Technology, University of Jinan, Jinan, Shandong Province 250022, China.
Bioorg Med Chem Lett. 2024 Dec 1;114:129986. doi: 10.1016/j.bmcl.2024.129986. Epub 2024 Oct 10.
Histone deacetylases (HDACs) are validated drug targets for various therapeutic applications. A series of Tetrahydro-β-carboline-based hydroxamate derivatives, designed as HDAC inhibitors (HDACis), were synthesized. Compound 11g exhibited strong inhibitory activity against HDAC1 and the A549 cancer cell line. Additionally, this compound increased the levels of acetylated histone H3 and H4. Notably, 11g effectively arrested A549 cells in the G2/M phase and also increased ROS production and DNA damage, thereby inducing apoptosis. Further molecular docking experiments illustrated the potential interactions between compound 11g and HDAC1. These findings suggested that the novel Tetrahydro-β-carboline-based HDACis could serve as a promising framework for further optimization as anticancer agents.
组蛋白去乙酰化酶 (HDACs) 是各种治疗应用的经过验证的药物靶点。一系列基于四氢-β-咔啉的羟肟酸衍生物被设计为 HDAC 抑制剂 (HDACi) 进行合成。化合物 11g 对 HDAC1 和 A549 癌细胞系表现出强烈的抑制活性。此外，该化合物增加了乙酰化组蛋白 H3 和 H4 的水平。值得注意的是，11g 有效地将 A549 细胞阻滞在 G2/M 期，并增加 ROS 产生和 DNA 损伤，从而诱导细胞凋亡。进一步的分子对接实验说明了化合物 11g 与 HDAC1 之间的潜在相互作用。这些发现表明，新型基于四氢-β-咔啉的 HDACi 可能成为进一步作为抗癌药物优化的有前途的框架。
