Click Synthesis of 1,2,3-Triazoles-Linked 1,2,4-Triazino[5,6-b]indole, Antibacterial Activities and Molecular Docking Studies

The reaction of 4,5-dihydro-3H-1,2,4-triazino[5,6-b]indole-3-thion with propargyl bromide, in EtOH at 80 degrees C, produces mono-propargylated 3-(prop-2-one-1-ylthio)-5H-1,2,4-triazino[5,6-b]indole. Further reaction of this compound with propargyl bromide, in DMF in the presence of K2CO3 at room temperature, produced successfully double-propargylated 5-(prop-2-one-1-yl)-3-(prop-2-one-1-ylthio)-5H-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-pi and pi-pi contacts with the active sites.