目的 設(shè)計(jì)、合成川芎嗪查爾酮類化合物并研究其抗乳腺癌活性。方法 以鹽酸川芎嗪為原料，通過酸堿中和、單氧化、重排、水解和醇羥基氧化制得重要中間體3，5，6-三甲基吡嗪-2-甲醛，再與芳乙酮發(fā)生Claisen-Schmidt羥醛縮合反應(yīng)合成川芎嗪查耳酮類化合物，接著用BBr₃進(jìn)行脫甲基得到了川芎嗪羥基查耳酮，并采用MTT法對目標(biāo)化合物進(jìn)行體外抗乳腺癌活性研究。結(jié)果 合成了21個(gè)川芎嗪查爾酮類化合物，其結(jié)構(gòu)均通過¹H-NMR和MS確證。生物活性結(jié)果測試表明，目標(biāo)化合物對乳腺癌MCF-7和MDA-MB-231細(xì)胞均有較強(qiáng)抑制活，并對MDA-MB-231細(xì)胞有更強(qiáng)的選擇抑制。其中查爾酮單元為二茂鐵的衍生物9t對MCF-7和MDA-MB-231展現(xiàn)出了最強(qiáng)的抑制活性；同時(shí)，這些川芎嗪查爾酮類化合物對正常乳腺上皮細(xì)胞MCF-10A均沒有毒性。結(jié)論 查爾酮是一個(gè)重要的抗腫瘤藥效團(tuán)，能夠提高川芎嗪的抗腫瘤活性，為今后發(fā)展新型、高效、低毒的具有抗腫瘤活性的川芎嗪衍生物提供了新思路。

Objective To design and synthesis of ligustrazine-chalcone derivatives and investigate their anti-breast cancer activities in vitro. Methods Ligustrazine hydrochloride was used as starting material to synthesize the important intermediate 3, 5, 6-trimethylpyrazine-2-formaldehyde through acid base neutralization, monooxidation, rearrangement, hydrolysis and hydroxyl oxidation reaction. Ligustrazine-chalcone derivatives were obtained underwent Claisen-Schmidt Aldol condensation by treatment of intermediate 3, 5, 6-trimethylpyrazine-2-formaldehyde with aromatic acetone, then the methoxyl of ligustrazine-chalcone derivatives were converted into hydroxylated ligustrazine-chalcone derivatives through application of demethylating reagent BBr₃. The anti-breast cancer activities were determined by MTT assays. Results Twenty-one ligustrazine-chalcone derivatives were synthesized and the structures have been confirmed by ¹H-NMR and MS spectra. The biological results showed that all synthesized ligustrazine-chalcone derivatives showed selective anti-breast cancer activity that has more potent against MDA-MB-231 cells than MCF-7. Specifically, ferrocenyl ligustrazine-chalcone compound 9t exhibited the greatest potency against both MCF-7 and MDA-MB-231. Moreover, these ligustrazine-chalcone derivatives were not toxic to normal cells. Conclusion Chalcone unit is a kind of important anti-tumor pharmacophore, which can enhance the anti-tumor effect of ligustrazine, and this study provides a new idea for the development of new, high-efficient and low-toxic ligustrazine derivatives with anti-tumor activity.