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目的研究15种番荔枝内酯类化合物对耐阿霉素乳腺癌细胞MCF-7/ADR的活性,并初步探讨其构效关系。方法MTT法检测15种番荔枝内酯化合物:annotemoyin-1(1)、annosquamin B(2)、annosquamin A(3)、annosquamin C(4)、annosquacin C(5)、urarigrandin A(6)、isodesacetyluvaricin(7)、annosquacin D(8)、annosquacin B(9)、12,15-cis-squamostatin-A(10)、squamostatin-A(11)、squamostanin-B(12)、squamostanin-A(13)、squamostatin-D(14)、squamostatin-E(15)对MCF-7/ADR细胞的抑制作用。结果所有受试化合物对MCF-7/ADR细胞均有强烈的抑制活性,且活性强于阳性药维拉帕米,化合物1的活性达到维拉帕米的190倍之多。结论四氢呋喃环与内酯环间的碳数越长,活性越强;链上羟基越多,活性越强;间双四氢呋喃型番荔枝内酯中,链上含有4个羟基的活性最强;相对构型为赤式的番荔枝内酯的活性比苏式的强,四氢呋喃环为反式构型的番荔枝内酯的活性比顺式的强。此外,相对分子质量为622,链上含有3个羟基,相对构型为赤式的邻双四氢呋喃型番荔枝内酯活性显著。
Objective To investigate the activity of 15 kinds of annona ester compounds against doxorubicin-resistant breast cancer cells MCF-7 / ADR and to explore its structure-activity relationship. Methods Fifteen kinds of annona compounds (annotemoyin-1 (1), annosquamin B (2), annosquamin A (3), annosquamin C (4), annosquacin C (5), urarigrandin A (6), isodesacetyluvaricin (7) annosquacin D (8) annosquacin B (9) 12,15-cis-squamostatin-A (10) squamostatin-A (11) squamostanin-B squamostatin-D (14), squamostatin-E (15) on MCF-7 / ADR cells. Results All the tested compounds had strong inhibitory activity on MCF-7 / ADR cells and were more active than the positive drug verapamil. The activity of compound 1 was 190 times that of verapamil. CONCLUSION: The longer the carbon number between the tetrahydrofuran ring and the lactone ring, the stronger the activity. The more the hydroxyl groups in the chain, the stronger the activity. In the bis-tetrahydrofuran type annona lactone, four hydroxyl groups are the most active in the chain; Annona eryngryptone, which is erythro-type, is more active than the threonine, and the annona lactone, which has the trans-form tetrahydrofuran ring, is more active than cis form. In addition, the relative molecular mass of 622, the chain contains three hydroxyl groups, the relative configuration of the ortho-dihydrofurane type Annona liana lactone activity significantly.