异噁唑衍生物的合成、抗肿瘤活性及分子对接研究

目的合成具有抗肿瘤活性的异噁唑类化合物。方法采用回流、氮气保护等条件,以中间体N-[[3-[3-氟-4-(1-哌嗪基)苯基]-4,5-二氢-5-异噁唑]甲基]乙酰胺的哌嗪基对位进行不同基团取代,合成异噁唑系列衍生物,并检测所得化合物的抗肿瘤活性。通过分子对接方法考察了合成化合物与Hsp90蛋白酶结合的模式。结果 12个新化合物的结构经1H-NMR确证。有6个化合物的肿瘤抑制率30%,根据分子对接结合模式找出了取代基的结构改造方向。结论合成的部分化合物具有抑制肿瘤的活性。

Study on synthesis, antitumor activity and molecular docking of isoxazole derivatives

Objective To synthetize the isoxazole compounds with antitumor activity. Methods The isoxazole derivatives were synthesized under the conditions of backflow and nitrogen protection. At the same time, the antitumor activities were tested. The interaction mode between synthetical compounds and Hsp90 protein was investigated by the molecular docking method. Results A total of 12 new compounds were obtained, and their structures were elucidated by ₁H-NMR technique. There were 6 compounds with tumor inhibitory rate exceeded 30%. A way of modifying substituent structure was shown on the basis of molecular docking model. Conclusion Some of the new compounds have antitumor activities.