目的 設(shè)計(jì)并合成紫羅蘭酮生物堿異噁唑類衍生物，結(jié)合活性篩選，發(fā)現(xiàn)具有活性的新型紫羅蘭酮生物堿衍生物。方法 制備（R）-紫羅蘭酮，在此基礎(chǔ)上經(jīng)過11步有機(jī)合成反應(yīng)制備紫羅蘭酮生物堿異噁唑衍生物。目標(biāo)衍生物經(jīng)核磁共振波譜和高分辨質(zhì)譜表征其化學(xué)結(jié)構(gòu)。通過乳腺癌細(xì)胞趨化遷移實(shí)驗(yàn)篩選衍生物的抗腫瘤轉(zhuǎn)移活性。結(jié)果 共制備8個(gè)目標(biāo)衍生物，經(jīng)抗腫瘤轉(zhuǎn)移活性篩選發(fā)現(xiàn)，化合物12c活性同Ion-31a相當(dāng)，強(qiáng)于陽性對(duì)照化合物PI3K抑制劑LY294002。結(jié)論 所有目標(biāo)衍生物均為新化合物，其中苯甲腈取代異噁唑化合物12c具有顯著抗腫瘤轉(zhuǎn)移活性。

Objective To design and synthesize the ionone alkaloid isoxazole derivative, and combine with activity screening, to find new bioactive derivatives of ionone alkaloid. Methods (R)-ionone was prepared, and the isooxazole derivative of ionone alkaloid were prepared after 11 steps of organic synthesis. The chemical structure of the target derivatives were characterized by nuclear magnetic resonance spectroscopy and high resolution mass spectrometry. The antitumor metastatic activities of the derivatives were screened by chemotactic migration of breast cancer cells. Results A total of 8 target derivatives were prepared. After screening for anti-tumor metastasis activitys, compound 12c was found had the same activity as Ion-31a, and was stronger than the positive control compound PI3K inhibitor LY294002. Conclusion All the targetderivatives are new compounds, and the benzonitrile substituted isoxazole compound 12c has significant anti-tumor metastasis activity.

R979.1

國家自然科學(xué)基金面上項(xiàng)目（81673310）；天津市自然科學(xué)基金資助項(xiàng)目（17JCZDJC32900）