| 摘要: | 受到資料庫中2-imino-1,2-dihydro-dipyrido[1,2-a:2′,3′-d] pyrimidin-5-one (IP) 抗癌活性的啟發，我們合成了一系列具有2-imino-1,2-dihydro-dipyrido[1,2-a:2′,3′-d] pyrimidin-5-one (IP) 的藥物GX002、GX003、GX004、GX006、GX007、GX008。接下來，我們進行了生物學研究，以測試它們對乳腺癌細胞的細胞毒性，並評估 GX006 的體內療效。一些 GX 化合物對三陰性乳腺癌細胞 MDA-MB-231 細胞具有良好的細胞毒性。綜上所述，GX化合物有一些對於三陰性乳癌細胞的增殖抑制是有效果的，在MDA-MB-21的細胞中，其IC50最低有到0.5至1μM。在這些化合物中，挑出GX006進行動物實驗，發現其對於腫瘤亦有不錯的抑制效果，表示這種藥物還具有潛力可開發出不同的結構來去測試對於癌細胞的治癒效果。;Inspired by the anti-cancer activity of 2-imino-1,2-dihydro-dipyrido[1,2-a:2′,3′-d] pyrimidin-5-one (IP) from in-house library, we synthesized a series of 2-imino-1,2-dihydro- dipyrido[1,2-a:2′,3′-d]pyrimidin-5-one (IP) containing compounds, GX002, GX003, GX004, GX006, GX007, GX008, with modifications of its functional groups. Next, we conducted biological study to test their cytotoxicity against breast cancer cells and evaluate the in vivo efficacy of GX006. Some of the GX compounds had good cytotoxicity to MDA-MB-231 cells, which are triple-negative breast cancer cells. Among of them, the IC50 value of cytotoxicity of the best one can reach around 0.5 to 1 μM. Furthermore, we chose the one, GX006, to the further animal study. The result showed that it can reduce the tumor growth significantly. In summary, this series of 2-imino-1,2-dihydro-dipyrido[1,2-a:2′,3′-d]pyrimidin -5-one containing compounds still have potential to develop into different candidates and study their inhibitory effect toward cancer cells. |
