作用於微小管抗癌藥物 2’,5’-dimethoxychalcone 衍生物之合成與活性評估SYNTHESIS AND BIOLOGICAL EVALUATION OF 2',5'-DIMETHOXYCHALCONE DERIVATIVES AS MICROTUBULE-TARGETED ANTICANCER AGENTS

專利類型

發明

專利國別 (專利申請國家)

中華民國

專利申請案號

099118967

專利證號

I 419687

專利獲證名稱

作用於微小管抗癌藥物 2’,5’-dimethoxychalcone 衍生物之合成與活性評估SYNTHESIS AND BIOLOGICAL EVALUATION OF 2',5'-DIMETHOXYCHALCONE DERIVATIVES AS MICROTUBULE-TARGETED ANTICANCER AGENTS

專利所屬機關 (申請機關)

高雄醫學大學

獲證日期

2013/12/21

技術說明

一系列2',5'-dimethoxychalcone之合成其中包括十八種新化合物，全部合成品進行對兩種人類癌細胞，NTUB1(人類膀胱癌細胞)及PC3(人類前列腺癌細胞)的抗癌試驗，結果除化合物21以外皆對NTUB1與PC3細胞具顯著地抗癌活性。其中C-4具有carbamoyl基團者對兩種癌細胞具強之抗癌活性。劑量1μM 13與17經與NTUB1細胞培養24時後對細胞週期會誘發G1期之停止並產生細胞凋亡死亡數增加。若各以劑量1μM與3μM之13與17分別與PC3細胞培養24h後，則13會引起S與G1期停止而17會引起G1及與G2/M期停止。這表示在NTUB1細胞內13與17雖具不同之carbamoyl基團在NTUB1細胞引起同樣之細胞分裂期之停止，但在PC3細胞內卻產生不同之細胞分裂期停止。化合物17與細胞培養後，癌細胞形成圓形或死亡，這與微小管之聚合有關。化合物17與NTUB1培養後，以西方點墨法分析其結果，呈現α-小管表現會隨17劑量增加而增加，此現象與paclitaxel之表現一樣，以上表示17與paclitaxel作用一樣，亦是一種微小管標靶抗癌藥物。 A series of novel 2´, 5´-dimethoxylchalcones compounds were syntheisized and evaluated their cytotoxicities and biological activities. All derivatives exhibited cytotoxic effect against NTUB1 and PC3 cells. Derivatives 17 was further performed the MTT assay of A549 and SV-HUC1 , found its specific cytotoxicity against cancer cells in urinary system and less toxicity for normal cells. Compounds 17 were assayed the cell cycle by flow cytometry and showed G2/M phase arrest and further induced apoptosis. Study indicated that more cells rounding up or dead associated with tubulin polymerization. Further 17 was used to be examined cell differetiation and tubulin polymerization by immunofluoresence and its molecular action was similar as taxol was. It was carried out the western blot analysis of α-tubulin in NTUB1 cells after treatment with various concentrations of 17 and taxol, and validated that 17 increasedα-tubulin level while taxol also increased α-tubulin level in the assay.

備註

連絡單位 (專責單位/部門名稱)

智財保護與科技管理組

連絡電話

07-3138030

網址