Du Cheng, Dong Ming-Hui, Ren Yu-Jie, Jin Lu, Xu Cheng
a School of Chemical and Environmental Engineering , Shanghai Institute of Technology , Shanghai 201418 , China.
J Asian Nat Prod Res. 2017 Sep;19(9):890-902. doi: 10.1080/10286020.2016.1250747. Epub 2016 Nov 3.
A new series of resveratrol heterocyclic analogs (4a-m) were designed and synthesized, and their inhibitiory effects on MCF-7 cells were evaluated to investigate structure-activity relationship. The effects of these analogs on human breast cancer MCF-7 cells were also determined. Results showed that MCF-7 cells could be inhibited more potently by these analogs than by resveratrol (IC = 80.0 μM). Among the analogs, compounds 4c, 4e, and 4k showed a significantly higher activity (IC = 42.7, 48.1, and 43.4 μM) than resveratrol. Furthermore, the derivatives without additional heterocyclic structure in the 4'-OH position exhibited a more potent activity than that with addition heterocyclic structure. In addition, docking simulation was performed to adequately position compound 4c in a human F-ATPase active site to determine a probable binding model. These heterocyclic analogs could be effective candidates for the chemoprevention of human breast cancer.
设计并合成了一系列新的白藜芦醇杂环类似物（4a - m），并评估了它们对MCF - 7细胞的抑制作用，以研究构效关系。还测定了这些类似物对人乳腺癌MCF - 7细胞的影响。结果表明，这些类似物对MCF - 7细胞的抑制作用比白藜芦醇更强（IC = 80.0 μM）。在这些类似物中，化合物4c、4e和4k表现出比白藜芦醇显著更高的活性（IC = 42.7、48.1和43.4 μM）。此外，在4'-OH位置没有额外杂环结构的衍生物比有额外杂环结构的衍生物表现出更强的活性。另外，进行了对接模拟，将化合物4c合理定位在人F - ATPase活性位点，以确定可能的结合模式。这些杂环类似物可能是人类乳腺癌化学预防的有效候选物。
