槐属生物碱和肉桂酸的分子杂合体的设计与合成作为潜在的抗肿瘤剂。
Design and Synthesis of Molecular Hybrids of Sophora Alkaloids and Cinnamic Acids as Potential Antitumor Agents.
机构信息
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
出版信息
Molecules. 2020 Mar 5;25(5):1168. doi: 10.3390/molecules25051168.
Twenty-five sophora alkaloids-cinnamic acid hybrids (including matrine-cinnamic acid hybrids, sophoridine-cinnamic acid hybrids, and sophocarpine-cinnamic acid hybrids) were designed, synthesized, and evaluated in vitro against three human tumor cell lines (HeLa, HepG2 and A549) with cisplatin as a positive control. Some matrine-cinnamic acid and sophoridine-cinnamic acid compounds exhibited potent effect against all three cancer cell lines, such as compounds , , , and . The structure-activity relationship study of the synthesized compounds was also performed. Preliminary mechanistic studies indicated that compounds and could induce apoptosis in HepG2 cell line. Further, compounds and altered mitochondrial membrane potential and produced ROS leading to cell apoptosis of HepG2 cells. Overall, our findings suggested that these compounds may provide promising lead compounds for further development as antitumor agents by structural modification.
设计、合成并评价了 25 种槐属生物碱-肉桂酸杂合体（包括苦参碱-肉桂酸杂合体、槐定碱-肉桂酸杂合体和氧化槐果碱-肉桂酸杂合体），以顺铂为阳性对照，对三种人肿瘤细胞系（HeLa、HepG2 和 A549）进行了体外评价。一些苦参碱-肉桂酸和槐定碱-肉桂酸化合物对所有三种癌细胞系均表现出很强的抑制作用，如化合物 、 、 、 。还对合成化合物进行了构效关系研究。初步的机制研究表明，化合物 和 可诱导 HepG2 细胞系凋亡。此外，化合物 和 改变线粒体膜电位并产生 ROS，导致 HepG2 细胞凋亡。总的来说，我们的研究结果表明，这些化合物可能通过结构修饰为进一步开发抗肿瘤药物提供有前途的先导化合物。
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