二氢青蒿素-查尔酮杂合物的设计、合成与抗肿瘤活性研究.pdfVIP

二氢青蒿素-查尔酮杂合物的设计、合成及抗肿瘤活性研究 ∗ 赵临襄 钟杭 刘丹 李明 丁贵军 赵璇 （沈阳药科大学制药工程学院，教育部基于靶点的小分子药物设计 与研究重点实验室，辽宁 沈阳 110016） 摘要：目的 设计合成一系青蒿素-查尔酮杂合物，提高二氢青蒿素对白血病细胞的生长抑制活性。方法 将取代查尔酮以醚键拼合到二氢青蒿素的 C-10 位，设计了 29 个青蒿素-查尔酮杂合物。采用细胞计数 法测定其对 HL-60 细胞的生长抑制作用。结果 合成了 29 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，其结构经 1H-NMR 、MS 和 IR 数据确证。所有目标化合物对 HL-60 细胞 都有不同程度的生长抑制作用。结论 所有目标化合物对 HL-60 细胞株的生长抑制活性均强于二氢青蒿 素，GI50 均小于 0.10μM 。但连接链的改变，查耳酮A 环和 B 环的调换及取代基的改变对活性的影响没 有显著差异。 关键词：二氢青蒿素；查尔酮；合成；生长抑制 Design, Synthesis and Antitumor Activity of Dihydroartemisinin-Chalcone Hybrids ZHAO Linxiang*, ZHONG Hang, LIU Dan, LI Ming, DING Guijun, ZHAO Xuan (School of Pharmaceutical Engineering, Key Laboratory of Structure-Based Drugs Design Discovery of Ministry of Education, Shenyang Pharmaceutical University , Shenyang 110016, China ) Abstract: Objective To design and synthesis a series of dihydroartemisinin-chalcone hybrids with improved antiproliferative effects in leukemia cells. Methods Twenty nine dihydroartemisinin-chalcone hybrids linked by ether were synthesized and investigated for their antiproliferative activity in human leukemia HL-60 cells. Results Twenty nine novel dihydroartemisinin derivatives were synthesized and their chemical structures 1 were confirmed by the application of H-NMR, MS and IR data. These DHA ethers have improved cell growth inhibitory effects in HL-60 cells. Conclusion All target compounds have improved cell growth inhibitory effects (GI500.10μM) in HL-60 cells compared to DHA. However, there is no significantly difference in inhibitory effects when changing the linker between dihydroartemisinin and chalcone, exchanging Ring A and Ring B of chalcone or altering a substituent of chalcone. Key words: dihy