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目的毛叶假鹰爪素C(Des-C)衍生物的进一步优化设计合成,及其抗肿瘤作用机制的初步探讨。方法结合已报道的毛叶假鹰爪素C衍生物,进行比较分子场法(CoMFA)分析,构建模型,指导设计新结构衍生物,对合成衍生物进行体外抗肿瘤细胞活性评价,验证模型有效性,运用流式细胞技术考察衍生物对细胞凋亡的影响。结果构建的模型可有效指导衍生物的设计合成并预测毛叶假鹰爪素C衍生物的活性,通过优化合成路线,得到10个新衍生物,对A549和HL60的抗肿瘤活性明显提高,并且可通过诱导细胞凋亡来发挥抗肿瘤作用。结论通过对先导物毛叶假鹰爪素C进行结构修饰和改造可有效提高化合物的抗肿瘤活性,初步明确了衍生物可通过诱导肿瘤细胞凋亡发挥抗肿瘤作用,为后续衍生物的研究提供方向和数据支持。
Objective To further optimize the design and synthesis of the derivatives of Desmopodin C (Des-C), and to explore their anti-tumor mechanism. Methods CoMFA analysis was performed in combination with the reported derivatives of the hairpin chelonin C, and the model was constructed to guide the design of new structural derivatives. The antitumor activity of the synthesized derivatives was evaluated in vitro and the model was validated The effects of derivatives on apoptosis were investigated by flow cytometry. Results The constructed model can effectively guide the design and synthesis of the derivatives and predict the activity of the derivatives of the hairy mites. By optimizing the synthetic route, 10 new derivatives were obtained and the antitumor activity of A549 and HL60 was significantly improved. Anti-tumor effect can be exerted by inducing apoptosis. Conclusions The structural modification and modification of the precursor vitexin C can effectively enhance the anti-tumor activity of the compound, and it has been initially clarified that the derivatives exert anti-tumor effects by inducing tumor cell apoptosis and provide the follow-up derivative research Direction and data support.