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

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 mu M). 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 mu M.

Automated summary

TNBC, the most aggressive subtype of breast cancer, has shown a significant increase of RAGE marker signal with malignant progression. Azeliragon, a RAGE inhibitor, has been shown to actively inhibit the TNBC cell line SUM149, while the newly synthesized compound KC-10 exhibited stronger inhibitory effects.