本篇研究將原先具有良好唾液酸轉移酶抑制活性的四吲哚 tetraindole） 衍生物 AMB04 作為起始結構，設計並合成一系列新型唾液酸轉移酶抑制 劑 為探討其結構–活性關係 structure–activity relationship， SAR）及其對三 陰性乳癌細胞株 MDA-MB-231 的生物活性，我們針對 tetraindole 骨架上 的四個吲哚上五號位的取代基以及中心苯環進行結構修飾。 在所有合成的化合物中，WR10 展現出最優異的體外唾液酸轉移酶抑 制活性，WR10 展現最佳的體外 ST 抑制活性，在 20 μM 下可完全抑制 ST6GAL1 活性 ， IC₅₀ 值為 11.75 μM 此外 ，在 MTT 細胞毒性實驗中 ， WR10 對 MDA-MB-231 細胞表現出顯著的細胞毒性，其 IC₅₀ 值為 7.06 μM。 最終研究結果顯示，tetraindole 骨架上細微的結構修飾即可顯著影響 ST 抑制活性 未來將進一步針對 WR10 進行更深入的生物活性評估，並 探討其對細胞唾液酸化機制的影響，以作為開發新型唾液酸轉移酶抑制劑 的基礎 。;Our group attempted to synthesize a new type of sialyltransferase (ST) inhibitor by modifying the indole-based tetraindole derivative AMB04， which previously exhibited potent ST inhibitory activity. To investigate the structure– activity relationship (SAR) of these ST inhibitors against the triple-negative breast cancer (TNBC) cell line MDA-MB-231， the four 5-substituted indole units and the central benzene ring of the tetraindole scaffold were modified. Among the synthesized compounds， WR10 exhibited the most potent ST inhibitory activity in vitro， achieving complete inhibition of ST6GAL1 activity at 20 μM， with an IC₅₀ value of 11.75 μM. Furthermore， WR10 showed significant cytotoxicity toward MDA-MB-231 cells in the MTT assay， with an IC₅₀ value of 7.06 μM. Overall， these findings demonstrate that subtle structural modifications can significantly influence the balance between enzymatic inhibition and cellular toxicity. Future studies will focus on advanced biological evaluations of WR10， as well as its impact on cellular sialylation mechanisms.
