Affiliated Hospital of Jinggangshan University, Center for Clinical Medicine Research of Jinggangshan University, Jinggangshan University, Ji'an, Jiangxi, China.
Center for Evidence-Based Medical and Clinical Research, First Affiliated Hospital of Gannan Medical University, Ganzhou, China.
J Enzyme Inhib Med Chem. 2023 Dec;38(1):2238137. doi: 10.1080/14756366.2023.2238137.
In this study, fourteen celastrol derivatives () were synthesised by esterification of celastrol at the 29th position. The anticancer activity of them was determined by the MTT assay. All the synthetic compounds showed significant antiproliferative activity against six cancer cells, with IC of the submicron molar level. The most promising compound ( blocked the cell cycle in the G2 phase and inhibited the expression of VEGF and MMP-9 in gastric cancer cell line MGC-803. In flow cytometry analysis, compound induced cancer cell apoptosis in a dose-dependent manner. In the mouse tumour xenograft model, compound showed significant anti-tumour activity at the dosage of 2.5 mg/kg and 1 mg/kg, with a higher inhibition rate than 5-FU (10 mg/kg). What's more, the anticancer mechanism involved in the inhibition of VEGF and the toxicity evaluation of compound were also investigated.
在这项研究中，通过酯化反应在雷公藤红素的 29 位合成了 14 种雷公藤红素衍生物（）。通过 MTT 测定法测定了它们的抗癌活性。所有合成的化合物对六种癌细胞均表现出显著的增殖抑制活性，IC 值在亚毫摩尔水平。最有前途的化合物（）阻断胃癌细胞系 MGC-803 中的细胞周期并抑制 VEGF 和 MMP-9 的表达。在流式细胞术分析中，化合物以剂量依赖的方式诱导癌细胞凋亡。在小鼠肿瘤异种移植模型中，化合物在 2.5mg/kg 和 1mg/kg 剂量下表现出显著的抗肿瘤活性，抑制率高于 5-FU（10mg/kg）。更重要的是，还研究了化合物抑制 VEGF 的抗癌机制和毒性评估。
