Click Synthesis of 1,2,3‐Triazoles‐Linked 1,2,4‐Triazino[5,6‐ <i>b</i> ]indole, Antibacterial Activities and Molecular Docking Studies
Ali Keivanloo, Saghi Sepehri, Mohammad Bakherad, Mahboobe Eskandari
Abstract
Abstract The reaction of 4,5‐dihydro‐3 H ‐1,2,4‐triazino[5,6‐ b ]indole‐3‐thion with propargyl bromide, in EtOH at 80 °C, produces mono‐propargylated 3‐(prop‐2‐one‐1‐ylthio)‐5 H ‐1,2,4‐triazino[5,6‐ b ]indole. Further reaction of this compound with propargyl bromide, in DMF in the presence of K 2 CO 3 at room temperature, produced successfully double‐propargylated 5‐(prop‐2‐one‐1‐yl)‐3‐(prop‐2‐one‐1‐ylthio)‐5 H ‐1,2,4‐triazino[5,6‐ b ]indole. The Cu(I)‐catalyzed click reaction of these propargylated compounds with different aromatic azides at room temperature, afforded new derivatives of 1,2,3‐triazoles‐linked 1,2,4‐triazino[5,6‐ b ]indole with high yields. The in vitro antibacterial activities of the novel 1,2,3‐triazoles were screened. The binding modes of these compounds to three enzyme active sites were determined by a molecular docking study. Docking studies demonstrated the most potent compounds; and binding maps revealed that the activities might be attributed to the hydrophobic interactions, hydrogen bonds, cation‐π and π‐π contacts with the active sites.