Design, synthesis, in silico and in vitro antimicrobial screenings of novel 1,2,4-triazoles carrying 1,2,3-triazole scaffold with lipophilic side chain tether

Abstract

Background1,2,4-Triazoles and 1,2,3-triazoles have gained significant importance in medicinal chemistry.ResultsThis study describes a green, efficient and quick solvent free click synthesis of new 1,2,3-triazole-4,5-diesters carrying a lipophilic side chain via 1,3-dipolar cycloaddition of diethylacetylene dicarboxylate with different surfactant azides. Further structural modifications of the resulting 1,2,3-triazole diesters to their corresponding 1,2,4-triazole-3-thiones via multi-step synthesis has been also investigated. The structures of the newly designed triazoles have been elucidated based on their analytical and spectral data. These compounds were evaluated for their antimicrobial activities. Relative to the standard antimicrobial agents, derivatives of 1,2,3-triazole-bis-4-amino-1,2,4-triazole-3-thiones were the most potent antimicrobial agents with compound 7d demonstrating comparable antibacterial and antifungal activities against all tested microorganisms. Further, the selected compounds were studied for docking using the enzyme, Glucosamine-6-phosphate synthase.ConclusionsThe in silico study reveals that all the synthesized compounds had shown good binding energy toward the target protein ranging from − 10.49 to − 5.72 kJ mol−1 and have good affinity toward the active pocket, thus, they may be considered as good inhibitors of GlcN-6-P synthase.

Design, Synthesis and Anticancer Screening of Novel Benzothiazole-Piperazine-1,2,3-Triazole Hybrids

“…As continuation of our previous study directed to design novel 1,4,5-trisubstituted-1,2,3-triazoles [ 34 , 35 , 36 ], we have adopted the optimized ecofriendly solvent free click procedure previously developed in our laboratory for the elaboration of two novel 4,5-diester-1,2,3-triazoles carrying benzothiazole-piperazine conjugate. The reaction required 1,3-dipolar cycloaddition reaction between the azide 3 with dimethyl/diethylacetylene dicarboxylate under neat conditions, in a water bath for 3 min, to afford the desired dimethyl/diethyl 1-(2-(4-(benzothiazol-2-yl)piperazin-1-yl)-2-oxoethyl)-1 H -1,2,3-triazole-4,5-dicarboxylate ( 6a , b ) in 92–94% yields.…”

Facile Syntheses and Molecular-Docking of Novel Substituted 3,4-Dimethyl-1H-pyrrole-2-carboxamide/carbohydrazide Analogues with Antimicrobial and Antifungal Properties

“…Molecular docking is an effective and reliable tool able to locate the probable binding interactions of ligands with their target proteins [ 33 , 34 ]. Recently, small chemical pharmacophores have been reported to inhibit cytochrome P450 sterol 14α-demethylase in a wide spectrum of fungal species [ 35 , 36 , 37 ]. To understand the mechanism of action and antifungal activity of our synthesized analogues, molecular docking studies were employed using the crystal structure of sterol 14α-demethylase (CYP51B, Protein Data Bank; pdb 5frb)) from a pathogenic filamentous fungus A. fumigatus [ 26 , 38 ].…”

DFT Study, POM Analyses and Molecular Docking of Novel Oxazaphosphinanes: Identification of Antifungal Pharmacophore Site

“…Computer-based molecular docking can facilitate the early stages of drug discovery through systematic prescreening of ligands (i.e., small molecules) for shape and energetic compatibility with a receptor (i.e., protein) prior to experimental evaluation [33][34][35]. Recently, small chemical ligands have been reported to inhibit cytochrome P450 sterol 14α-demethylase in a wide spectrum of fungal species [36][37][38]. To understand the mechanism of action and antifungal activity of our synthesized analogues, molecular docking studies were employed using the crystal structure of human cytochrome P450 2E1 that was picked from the Protein Data Bank (CYP2E1; pdb code: 3e4e) (http://www.rcsb.org/pdb).…”