青蒿素类化合物抗肿瘤机制研究- 青蒿素类化合物/转铁蛋白对接研究

本文采用柔性分子对接技术, 将11个青蒿素类化合物对接到在不同分离度下测出转铁蛋白结构的活性腔内, 研究其抗肿瘤机制, 运用多种打分函数对结果进行打分。从对接结果可看出, 转铁蛋白结构中键合铁的Asp-63、Tyr-188和His-249残基以及稳定键合位点的Arg-124和Lys-296残基与青蒿素小分子的距离小于0.5 nm, 活性大的化合物得分较高。对接后的模型解释了转铁蛋白的存在促使Fe²⁺与青蒿素作用、青蒿素不参与其他的代谢、增加青蒿素细胞毒性的机制, 为设计、合成全新青蒿素类化合物打下了良好的基础。

Antitumor mechanism of Qinghaosu derivatives — molecular docking studies of Qinghaosu derivatives with transferrin

To investigate the antitumor mechanism of artemisninin, a flexible docking analysis was used to score all kinds of functions of 11 Qinghaosu derivatives and transferrin with different resolutions.  The distances  of Asp-63, Tyr-188, His-249, Arg-124 and Lys-296 with Qinghaosu were less than 0.5 nm, separately.  Meanwhile,  the higher is the activity of Qinghaosu derivatives the higher is the score.  Our model explains that Fe²⁺ is more feasible to react with Qinghaosu, and not involved in other metabolism in presence of transferrin.  Docking results unveil that Iron(Ⅱ)-transferrin increased the cytotoxicity of Qinghaosu derivatives and provide a rational basis for further design and synthesis of novel Qinghaosu derivatives.