Design, synthesis and anti-TNBC activity of Azeliragon triazole analogues

  • Bioorg Med Chem Lett. 2021 Dec 15:54:128444. doi: 10.1016/j.bmcl.2021.128444.
Jizhao Xie  1 ,  Huanji Xu  2 ,  Xinduo Wu  2 ,  Yunfeng Xie  2 ,  Xiuhong Lu  3 ,  Lisheng Wang  4
Affiliations
  • 1. Medical College, Guangxi University, Nanning 530004, China; School of Pharmaceutical Science, Guangxi Medical University, Nanning 530021, China.
  • 2. School of Pharmaceutical Science, Guangxi Medical University, Nanning 530021, China.
  • 3. Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China. Electronic address: [email protected].
  • 4. Medical College, Guangxi University, Nanning 530004, China. Electronic address: [email protected].
PMID: 34763082 DOI: 10.1016/j.bmcl.2021.128444
Abstract

Triple-negative breast Cancer (TNBC) is the most aggressive subtype of breast Cancer. Many studies have shown a significant increase in the marker signal of the receptor for advanced glycation end-products (RAGE) with the malignant progression of tumor growth, metastasis and recurrence of breast Cancer, including TNBC of primary tumors and lymph node metastases. Azeliragon is a RAGE inhibitor and it has been shown to actively inhibit the TNBC cell line, SUM149 (IC50 = 5.292 ± 0.310 μM). In order to develop a new anti-TNBC agent, we designed, synthesized and screened 26 Azeliragon triazole analogues to determine their anti-TNBC activities in vitro. The most active compound was KC-10 with an IC50 value of 0.220 ± 0.034 μM.

Keywords
Azeliragon; RAGE inhibitor; SUM149; Triazole analogue; Triple-negative breast cancer.