唾液酸轉移酶的過度表現是細胞組織的生物過程,在許多生理上和病理上扮演重要的角色,例如;細胞間的黏附、癌症轉移及感染息息相關,所以本實驗室嘗試去改善由石膽酸-天門冬胺酸為骨幹,包含長鏈、芳香環以及醣類衍生物,做為唾液酸轉移酶抑制劑,探討其抑制癌細胞轉移之效果,其中,更發現化合物9對於乳癌細胞實驗中,抑制MDA-MB-231 cells這株癌細胞效果IC50值達到21.97 ± 2.2 μM,除此之外,對於α2-6N 唾液酸轉移酶的IC50為5.86μM,對於α2-3N 唾液酸轉移酶的效果更是好為2.86 μM,已經達到接近nM的等級;在MTT assay中,當化合物9 濃度增加到100μM時,幾乎沒有任何毒殺效果,更進一步證明可以有效的抑制癌細胞的轉移。
Overexpression of sialyltransferase is vital biological process, which plays a role in various physiological and pathological events, such as cell-cell adhesion, immune defense, tumor cell metastasis, invasions, and inflammation. To increase the inhibitory potency of sialyltransferase, we prepared a series of O-Asp-lithocholic acid derivatives with variable functional moieties including 4-nitrobenzoic acid, aliphatic chain, sugar and aromatic ring. Among the evaluations of sialyltransferase inhibition, we find the compound 9 was the most active compound with an IC50 of 5.86 μM and 2.86μM 3.6 towardα2-6N andα2-3N sialyltransferases, respectively. For MDA-MB-231 cell line, compound 9 was found to have negligible effect on growth inhibition in the range 0~100