College of Public Basic Sciences, Jinzhou Medical University, Jinzhou 121001, China.
School of Chemical and Environmental Engineering, Liaoning University of Technology, Jinzhou 121001, China.
Molecules. 2019 Oct 8;24(19):3631. doi: 10.3390/molecules24193631.
Novel 18β-glycyrrhetinic acid derivatives possessing a carbamate moiety and structurally similar ester derivatives were developed and evaluated for their efficacy as antitumor inhibitors. In the cellular assays, most of the -substituted carbamate derivatives at the C3-position exhibited potent activities. The results of SAR investigation revealed that the introduction of the morpholine group at the C30-COOH led to a significant loss of the inhibitory potency. Among the ester derivatives, the ester group at C3-position also determined a noticeable reduction in the efficacy. Compound 3j exhibited the most prominent antiproliferative activity against six human cancer cells (A549, HT29, HepG2, MCF-7, PC-3, and Karpas299). Furthermore, compound 3j exerted a moderate inhibiting effect on the ALK. The results of molecular docking analyses suggested that it could bind well to the active site of the receptor ALK, which was consistent with the biological data. These results might inspire further structural optimization of 18β-glycyrrhetinic acid aiming at the development of potent antitumor agents. The structures , , , , and were studied by X-ray crystallographic analyses.
开发并评价了具有氨基甲酸酯部分的新型 18β-甘草次酸衍生物和结构相似的酯衍生物，以评估它们作为抗肿瘤抑制剂的功效。在细胞测定中，C3 位取代的 -氨基甲酸酯衍生物大多数表现出很强的活性。SAR 研究的结果表明，在 C30-COOH 处引入吗啉基导致抑制活性显著丧失。在酯衍生物中，C3 位的酯基也决定了功效的明显降低。化合物 3j 对六种人癌细胞（A549、HT29、HepG2、MCF-7、PC-3 和 Karpas299）表现出最显著的增殖抑制活性。此外，化合物 3j 对 ALK 具有适度的抑制作用。分子对接分析的结果表明，它可以与受体 ALK 的活性位点结合良好，这与生物学数据一致。这些结果可能会激发对 18β-甘草次酸的进一步结构优化，以开发有效的抗肿瘤药物。通过 X 射线晶体学分析研究了结构 、 、 、 和 。
