Synthesis of Amino Acid-comprising Sialyltransferase Inhibitors and Their Antimetastatic Activities against Human Breast Cancer Cells

• Published in: Journal of the Chinese Chemical Society (Taipei) 2016-02, Vol.63 (2), p.171-180
• Main Authors: Fu, Chih-Wei, Chang, Kai-Hsuan, Jen, Ya Ching, Chang, Tzu Ting, Li, Wen-Shan
• Format: Article
• Language: English
• Subjects: Amino acid-containing lithocholic acids; Antiproliferative effect; Cell migration; Human sialyltransferase inhibitors; Wound healing
• ISSN: 0009-4536; 2192-6549
• DOI: 10.1002/jccs.201500348

The amino acid‐containing lithocholic acids (LCA) represent a new class of human sialyltransferase (ST) inhibitors. In this study, we have reported their design, synthesis, and inhibitory activity against human STs. Among these derivatives, D‐Glu‐LCA 7, L‐Asp‐L‐Asp‐LCA 13, and L‐Asp‐L‐Asp‐Gly‐Gly‐LCA 22 with specific amino acid sequence were the most active ones with IC50 values of 2.3–5.6 and 4.2‐6.2 μM toward α‐2,3‐ST and α‐2,6‐ST, respectively. The current study demonstrates that the new class of ST in‐ hibitors inhibit cell migration in breast cancer cells by preventing closure of the wound rather than involv‐ ing a direct antiproliferative effect. Development of amino acid sequence‐dependent ST inhibitors was achieved and some of these inhibitors were found to have significant effect in not only suppression of α‐2,3‐ST and α‐2,6‐ST activities but also inhibition of breast cancer cell migration.