Guizhou University, Huaxi Avenue South, Guiyang 550025, China.
State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, 3491 Baijin Road, Guiyang 550014, China.
Molecules. 2019 Nov 15;24(22):4138. doi: 10.3390/molecules24224138.
Twenty-seven L-shaped ortho-quinone analogs were designed and synthesized using a one pot double-radical synthetic strategy followed by removing methyl at C-3 of the furan ring and introducing a diverse side chain at C-2 of the furan ring. The synthetic derivatives were investigated for their cytotoxicity activities against human leukemia cells K562, prostate cancer cells PC3, and melanoma cells WM9. Compounds , , , , , , , , , , , , , and exhibited a better broad-spectrum cytotoxicity on three cancer cells. and selectively displayed potent inhibitory activities on leukemia cells K562 and prostate cancer cells PC3, respectively. Further studies indicated that , , , , and could significantly induce the apoptosis of PC3 cells. and significantly induced apoptosis of K562 cells. , , and induced significant apoptosis of WM9 cells. The structure-activity relationships evaluation showed that removing methyl at C-3 of the furan ring and introducing diverse side chains at C-2 of the furan ring is an effective strategy for improving the anticancer activity of L-shaped ortho-quinone analogs.
设计并合成了 27 个 L 型邻醌类似物，采用一锅双自由基合成策略，随后在呋喃环的 C-3 位脱甲基，并在呋喃环的 C-2 位引入不同的侧链。研究了这些合成衍生物对人白血病细胞 K562、前列腺癌细胞 PC3 和黑色素瘤细胞 WM9 的细胞毒性活性。化合物 、 、 、 、 、 、 、 、 、 、 、 和 对三种癌细胞表现出更好的广谱细胞毒性。 和 对白血病细胞 K562 和前列腺癌细胞 PC3 分别表现出选择性的强抑制活性。进一步的研究表明， 、 、 、 和 可显著诱导 PC3 细胞凋亡。 和 可显著诱导 K562 细胞凋亡。 、 和 诱导 WM9 细胞明显凋亡。构效关系评价表明，去除呋喃环 C-3 位的甲基并在呋喃环 C-2 位引入不同的侧链是提高 L 型邻醌类似物抗癌活性的有效策略。
