Lan Hailang, Zhu Xiaping, Lin Guishan, Duan Wengui, Cui Yucheng, Li Fangyao, Li Dianpeng
School of Chemistry and Chemical Engineering, Guangxi University, Nanning, 530004, Guangxi, P. R. China.
College of Pharmacy, Guilin Medical University, Guilin, 541100, China.
Chem Biodivers. 2023 Mar;20(3):e202201163. doi: 10.1002/cbdv.202201163. Epub 2023 Feb 6.
Twenty novel longifolene-derived tetraline fused thiazole-amide compounds were synthesized from longifolene, a renewable natural resource. Their structures were characterized by FT-IR, NMR, ESI-MS, and elemental analysis. The in vitro antiproliferative activity of these compounds against SK-OV-3 ovarian cancer cell lines, MCF-7 human breast cancer cell lines, HepG2 human liver cancer cell lines, A549 human lung adenocarcinoma cell lines, and T-24 human bladder cancer cell lines was tested by MTT assay. Compounds 6a-6c displayed significant and broad-spectrum antiproliferative activity against almost the tested cancer cell lines with IC in the range of 7.84 to 55.88 μM, of which compound 6c exhibited excellent antiproliferative activities with 7.84 μM IC against SKOV-3, 13.68 μM IC against HepG2, 15.69 μM IC against A549, 19.13 μM IC against MCF-7, and 22.05 μM IC against T-24, showing better and broad-spectrum antiproliferative effect than that of the positive control 5-FU. Furthermore, the action model was analyzed by the molecular docking study. Some intriguing structure-activity relationships were found and discussed herein by DFT theoretical calculation.
从可再生自然资源长叶烯出发，合成了20种新型的长叶烯衍生四氢萘并噻唑 - 酰胺化合物。通过傅里叶变换红外光谱（FT - IR）、核磁共振（NMR）、电喷雾电离质谱（ESI - MS）和元素分析对其结构进行了表征。采用MTT法测试了这些化合物对SK - OV - 3卵巢癌细胞系、MCF - 7人乳腺癌细胞系、HepG2人肝癌细胞系、A549人肺腺癌细胞系和T - 24人膀胱癌细胞系的体外抗增殖活性。化合物6a - 6c对几乎所有测试的癌细胞系均表现出显著的广谱抗增殖活性，IC50值在7.84至55.88 μM范围内，其中化合物6c表现出优异的抗增殖活性，对SKOV - 3的IC50为7.84 μM，对HepG2为13.68 μM，对A549为15.69 μM，对MCF - 7为19.13 μM，对T - 24为22.05 μM，显示出比阳性对照5 - FU更好的广谱抗增殖效果。此外，通过分子对接研究分析了作用模式。通过密度泛函理论（DFT）计算发现并讨论了一些有趣的构效关系。
