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目的设计合成一系列含有查尔酮侧链的二氢青蒿素衍生物,提高二氢青蒿素对白血病细胞的生长抑制活性。方法将取代查尔酮及其类似物拼合到二氢青蒿素的C-10位,设计28个查尔酮取代二氢青蒿素衍生物。采用细胞计数法测定其对HL-60、P388和P388/Adr细胞的生长抑制作用。结果与结论合成了28个含有查尔酮侧链的二氢青蒿素衍生物,均为未见文献报道的新化合物,其结构均经1H-NMR、MS和IR确证。所有目标化合物对HL-60、P388和P388/Adr细胞都有不同程度的生长抑制作用,初步构效关系分析结果:青蒿芳香醚类化合物的抗增殖活性好于青蒿脂肪醚类化合物,取代查尔酮侧链中的α,β-不饱和酮结构并不是影响抗增殖活性的必需基团,双键还原和全部还原产物活性相当。化合物5d对HL-60细胞的生长抑制作用最强,化合物7a、7 c和7 e对HL-60、P388和P388/Adr细胞均表现出显著的生长抑制活性,值得深入研究。
OBJECTIVE To design and synthesize a series of dihydroartemisinin derivatives containing chalcone side chains to enhance the growth inhibitory activity of dihydroartemisinin on leukemia cells. Methods The substituted chalcone and its analogues were assembled into the C-10 position of dihydroartemisinin, and 28 chalcone substituted dihydroartemisinin derivatives were designed. The growth inhibition of HL-60, P388 and P388 / Adr cells was measured by cell counting. RESULTS AND CONCLUSIONS A total of 28 dihydroartemisinin derivatives with chalcone side chains were synthesized and all of them were new compounds reported in the literature. Their structures were confirmed by 1H-NMR, MS and IR. All the target compounds had different degrees of growth inhibitory effects on HL-60, P388 and P388 / Adr cells. The preliminary structure-activity relationship analysis showed that the anti-proliferative activity of Artemisia annua ethers was better than Artemisia annua ethers. The α, β-unsaturated ketone structure in the chalcone side chain is not an essential group that affects antiproliferative activity, and the double bond reduction is comparable to the activity of all the reduced products. Compound 5d showed the strongest growth inhibitory effect on HL-60 cells. Compounds 7a, 7c and 7e showed significant growth inhibitory activity on HL-60, P388 and P388 / Adr cells, which deserved further study.