A Simple Work-Up-free, Solvent-free Approach to Novel Amino Acid Linked 1,4-Disubstituted 1,2,3-Triazoles as Potent Antituberculosis Agents

Abstract

An efficient, green strategy for synthesis of 1,4-disubstituted-1,2,3-triazole has been developed using 1,8-diazabicyclo[5.4.0]­undec-7-ene (DBU) acetate ionic liquid (200 μL) under a solvent- and external base-free condition. This protocol is further applied for the synthesis of novel amino acid containing 1,2,3-triazole molecules, which were then evaluated for potential antitubercular and antibacterial activities. Cytotoxicity assay of the compounds was also performed. In silico analysis of the promising compounds selected through experimental analysis was thereafter performed for visualizing molecular interactions and predicting binding affinities between our synthesized molecules, which exhibited good activity in experimental studies and the DprE1 target protein of Mycobacterium tuberculosis. Durg-likeness studies also show potential of the synthesized molecules as drug candidates.

Design and Synthesis of Quinazolinone-Triazole Hybrids as Potent Anti-Tubercular Agents

“…The anti-TB activities of the synthesized compounds were performed following literature procedures. ,, …”

“…The growth of M. tuberculosis was found to be inhibited by vasicine analogues such as vasicinone, vasicine acetate, 2-acetyl benzylamine, bromhexine, ambroxol, etc. − Similarly, numerous antibacterial drugs contain a 1,2,3-triazole moiety . Various 1,2,3-triazoles have been reported recently with good to excellent anti-TB activity; e.g., I-A09, a drug with a 1,2,3-triazole moiety, is a lead anti-TB agent presently in clinical trials. − Halogen bonds formed between proteins and their ligands have been widely employed in drug design because of their role in improving ligand binding affinities. In particular, fluorine increases the lipophilicity of compounds, which in turn enhances cell membrane penetration. − Considering the aforementioned points, we have designed quinazolinone–triazole hybrids that were expected to show better anti-TB activity than the existing anti-TB drugs.…”

[Et3NH][HSO4] catalyzed solvent‐free synthesis of new 1,2,3‐triazolidene‐indolinone derivatives

“…[4] The synthetically available basic heterocyclic scaffold of 1,2,3-triazole has found a broad spectrum of applications in the field of drug designing and synthesis. [5] The 1,2,3-triazoles have attracted much more interest due to their extensive biological and pharmaceutical properties, including anticancer, [6] antitubercular, [7] antiinflammatory, [8] antioxidant, [9] antifungal, [10] and antibacterial. [11] The 1,2,3-triazole nucleus is featured in marketed drugs (Figure 1).…”

CuO–NiO bimetallic nanoparticles supported on graphitic carbon nitride with enhanced catalytic performance for the synthesis of 1,2,3‐triazoles, bis‐1,2,3‐triazoles, and tetrazoles in parts per million level

“…Exploration of wide range of procedures in catalysis to eliminate and deter harsh reaction conditions are constantly in practice. Recent reported methodologies includes DBU catalyzed triazoles in ionic liquids, [ 28 ] magnetic NPs supported Cu(I) catalyst, [ 29 ] bentonite clay supported cuprous iodide NPs, [ 30 ] spin‐canted CuFe 2 O 4 NPs, [ 31 ] and Cu/Al 2 O 3 surface under ball milling condition. [ 32 ]…”