| Abstract: | 本論文是延續本實驗室先前的研究(EJMC, 2009, 44(6), 2552-2562)，都是合成2-苯乙烯色素母酮衍生物並作一系列的抗癌實驗。起先本論文是著重在2-苯乙烯色素母酮B環結構的改變，接著固定B環改變A環結構。根據先前所述，我們利用三個步驟合成2-苯乙烯色素母酮衍生物52a-q，並將這17個化合物進行一系列的抗癌細胞增生實驗(表2-5)。
有趣的是化合物52d (4’-methoxy group)、52l (3’,4’-difluoro group)、52q (3’,4’,5’-trimethoxy group)都有不錯的抗癌細胞增生效果，其GI50介在2到23μΜ之間。由於52q (3’,4’,5’-trimethoxy group)對AGS(胃癌細胞)擁有高度的選擇性及抑制性，故我們將B環固定為3’,4’,5’-三甲氧基(3’,4’,5’-trimethoxy group)，接著改變A環上甲氧基(methoxy group)取代基的位置，合成出2-苯乙烯色素母酮衍生物 52r-v，其衍生物在AGS細胞的抗癌細胞增生活性GI50值介於1.3到24μΜ之間。另外，我們將 52q 到 52v 的結構利用三溴化硼(boron tribromide，BBr3)作去甲基化反應(demethylation)得到多重羥基(polyhydroxyl group)衍生物 55a-e，但令我們驚訝的是 55a-e 在抗癌細胞增生實驗中其對所有的癌細胞完全沒有任何抑制生長能力。
總結以上結果，可證明2-苯乙烯色素母酮衍生物之所以有抗癌細胞增生活性的原因是2-苯乙烯色素母酮衍生物與癌細胞作用時會產生有利的立體電子效應(stereoelectronic effects)和疏水性(hydrophobicity)基團帶來適當的活性。
Previously, we have synthesized a series of 2-styrylchromones that exhibited anticancer effect against carcinoma cells (EJMC, 2009, 44(6), 2552-2562). In this study, we initially focused on the structural modific- ations on B-ring while A-ring was free of substitution. The synthetic route of 2-styrylchromones was carried out in three steps that afforded 52a-q based on the abovementioned work. With seventeen analogs in hand, we examined their growth inhibition on a panel of carcinoma cell lines.
Interestingly, 52d, 52l and 52q bearing 4’-methoxy, 3’,4’-difluoro and 3’,4’,5’-trimethoxy groups showed superior antiproliferative effect against all cell lines with GI50 values between 2 to 23μM. Due to the higher sensitivity of AGS in response to 52q-mediated growth inhibition, the 3’,4’,5’-trimethoxy groups on B-ring of 52q were remained while A-ring was modified with methoxy groups at different positions that obtained with 52r-v. All analogs exhibited antiproliferative effect against AGS cell line with GI50 values of 1.3 to 24 μM. Further demethylation of 52q to 52v mediated by boron tribromide (BBr3) afforded polyhydro- xyl derivatives 55a–e. To our surprise, none of them exhibited growth inhibitory effect against all cell lines. In summary, we demonstrated that the antiproliferative effect induced by 2-styrylchromes may be attribute- able to stereoelectronic effects as well as hydrophobicity for appropriate activity. |
