Dept. de Química Inorgánica y Orgánica, Universidad Jaume I, E-12071 Castellón, Spain.
Dept. de Química Inorgánica y Orgánica, Universidad Jaume I, E-12071 Castellón, Spain.
Bioorg Med Chem. 2019 Mar 1;27(5):880-887. doi: 10.1016/j.bmc.2019.01.039. Epub 2019 Jan 30.
Twenty-four derivatives structurally related to honokiol have been synthesized and biologically evaluated. IC values were determined towards the HT-29, MCF-7 and HEK-293 cell lines. Some of these derivatives exhibited comparable or lower IC values than honokiol towards the HT-29 and MCF-7 cell lines or else higher selectivity indexes than the natural product. Twelve selected derivatives were evaluated for their ability to inhibit the expression of the VEGFA, hTERT and c-Myc genes and also to inhibit the production of total c-Myc protein and the secretion of the VEGF protein. One of the most promising compounds, 3-(2,4-dimethoxyphenyl)pyridine, may be a good candidate for further studies as an anticancer agent as it is able to improve the effect shown by honokiol in downregulating all gene expression and protein production at a safe concentration for non-tumor cells.
已经合成了 24 种与厚朴酚结构相关的衍生物，并对其进行了生物学评价。测定了它们对 HT-29、MCF-7 和 HEK-293 细胞系的 IC 值。这些衍生物中的一些在 HT-29 和 MCF-7 细胞系中表现出与厚朴酚相当或更低的 IC 值，或者比天然产物具有更高的选择性指数。选择了 12 种衍生物来评估它们抑制 VEGFA、hTERT 和 c-Myc 基因表达的能力，以及抑制总 c-Myc 蛋白产生和 VEGF 蛋白分泌的能力。其中一种最有前途的化合物 3-(2,4-二甲氧基苯基)吡啶，可能是一种很好的候选药物，因为它能够增强厚朴酚在下调所有基因表达和蛋白质产生方面的作用，而在非肿瘤细胞中使用安全浓度。
