Synthesis of New Bis‐1,2,3‐Triazoles Possessing High Anti‐Proliferative Activities and Electrochemical Interaction Studies With dsDNA

ABSTRACT In this study, new bis‐1,2,3‐triazole derivatives (4a–h) were synthesized with 60%–95% yield by reacting N,N'‐(4,5‐dichloro‐1,2‐phenylene)bis(2‐azidoacetamide) with various alkyne compounds in the presence of CuSO 4 .5H 2 O and sodium ascorbate. The in vitro anti‐proliferative activity of the products was evaluated against prostate (PC3 cells) and breast cancer (SKBR3 cells), along with normal retinal pigment epithelial ARPE‐19 cells to assess their cytotoxic effects. 4e , 4f , and 4a showed notable anti‐proliferative activities against PC3 cells, with IC50 values of 10.89, 12.49, and 36.13 µM, respectively, while the reference drug cisplatin showed anti‐proliferative activity with IC50 value of 10.5 µM. 4e also showed remarkable anti‐proliferative activity compared with the reference drug cisplatin (IC50 = 15.0 µM) against SKBR3 cells with an IC50 value of 14.05 µM. Hoechst DNA staining revealed that compound 4e induced cell death in prostate cancer cells by mediating in a dose‐dependent manner. Electrochemical methods were used to study DNA interactions of 4a , 4e , and 4f , using differential pulse voltammetry and cyclic voltammetry. Consequently, binding coefficients for 4a , 4e , and 4f were found to be 6.7x10 3 , 9.12x10 2 , and 2.8x10 6 M −1 , respectively. Molecular docking simulations predicted that the most potent compound 4e interacts with the minor groove of DNA.