第一部分：我們合成了具有代表性的天然物結構所衍生出的2-苯乙烯色素母酮衍生物，利用了簡單的合成方法來合成，並作為新型抗癌試劑的模板，以測試其細胞毒殺性(cytotoxicity)及作用機轉。經由生物活性的試驗後證實化合物38可抑制子宮頸癌細胞(HeLa Cell)生長並誘導細胞凋亡(apoptosis)，IC50值可達到4.9 μM。 第二部份：我們利用Mannich類型反應設計出8-羥基喹啉衍生物，並藉由修飾化合物90來合成出一系列8-羥基喹啉衍生物，來研究其分子結構與抗癌活性的關係(Structure-Activity Relationship)。經由生物活性的測試後證實可抑制一系列的癌細胞株生長。而最具抑制生長活性的化合物115，IC50值可達到0.7 μM。 The first part : A series of 2-styrylchromone analogs were synthesized and examined for their antiproliferative effects on a panel of carcinoma cells. Among the tested agents, only 34 exhibited a moderate activity with an IC50 value of 28.9 μM against PC-3 cells which indicates the selectivity of PC-3 cells in response to 2-styrylchromones. In addition, 38 demonstrated the most antiproliferative effect with an IC50 value of 4.9 μM against HeLa cells. Together, these results suggest a potential structural optimization and pharmacological study of 2-styrylchromones.
The second part : A series of Mannich-type reaction of 8-hydroxyquinoline derivatives are prepared which demonstrated apoptosis-inducing effect against HeLa cervical cancer cells. Among the tested compounds, 5-nitro-7-((4-tosylpiperazin-1-yl)methyl)quinolin-8-ol (115) exhibited the most anti-proliferative effect with an IC50 value of 0.7 μM. Further structure-activity relationship (SAR) study as well as pharmacological exploitation of this novel 8-hydroxyquinoline scaffold are underway.
