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

Abstract

The reaction of 4,5-dihydro- 3H-1,2,4-triazino[5,6-b]indole-3-thion with propargyl bromide, in EtOH at 80°C, produces monopropargylated 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 K 2 CO 3 at room temperature, produced successfully double-propargylated 5-The Cu(I)-catalyzed click reaction of these propargylated compounds with different aromatic azides at room temper-ature, afforded new derivatives of 1,2,3-triazoles-linked 1,2,4triazino [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. Figure 7. Binding mode of compound 7 a (A), 7 b (B) and 7 c (C) in the active site. ChemistrySelectFull Papers

An Overview of Recent Advances in Biomedical Applications of Click Chemistry

“…In addition, derivatives, 6c (X = 2-Cl;3-NO 2 ), 6d (X = 3-NO 2 ;5-Cl), and 7d were found to be most active against M. luteus, S. aureus, and E. coli, respectively, as compared to the reference drug, Tetracycline. 84 There has been extensive clinical use of metronidazole (MTZ), an imidazole derivative, for the treatment of Grampositive and Gram-negative bacterial infections in the past few years. In an experiment done by Negi and co-workers, the effectiveness of 35 different metronidazole−triazole hybrids was examined against methicillin-resistant S. aureus and compared with a standard drug, oxacillin (Scheme 9).…”

Application of “Click” Chemistry in Biomedical Hydrogels

“…These advantages are undoubtedly the dream of drug preparation. Therefore, “click” chemistry has attracted much attention in the field of drug synthesis . Because the original “click” reaction relies on copper ions that are toxic to organisms, it has not been frequently used in the field of medicine.…”

“…Therefore, “click” chemistry has attracted much attention in the field of drug synthesis. 103 Because the original “click” reaction relies on copper ions that are toxic to organisms, it has not been frequently used in the field of medicine. However, with the development of “click” chemistry and the introduction of various copper-free “click” chemistry reactions, “click” chemistry has become very popular in the field of biomedicine, as well as for drug synthesis.…”

Novel 1,2,3-triazole-1,4-dihydropyridine-3,5-dicarbonitrile derivatives: synthesis and antibacterial evaluation

“…Some of these derivatives were found to bind to active sites of dihydrodipicolinate reductase of Escherichia coli, undecaprenyl diphosphate synthase (UPPS) of Micrococcus luteus and fibrinogen-binding MSCRAMM, clumping factor A Staphylococcus aureus via hydrogen bonds and hydrophobic interactions, respectively. 24 Methyl derivative of acridone-1,2,3-triazole displayed significant antibacterial activity against Staphylococcus aureus (MRSA) with MIC:19.6 µg mL -1 and it also played a key role in bond interaction with Ala 7 and hydrophobic interaction into DHFR active site of dihydropteroate synthase (DHPS) in methicillin-resistant Staphylococcus aureus (MRSA). Most of the tested compounds displayed moderate activity against Escherichia coli and Klebsiella pneumoniae with the MIC values between 56.6 -74.0 μg mL -1 .…”