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2,4,5-Triaryl-1H-imidazole hybrids were synthesized from substituted benzil and indole-3-aldehyde which on subsequent treatment with aryl azides converted to 1,2,3-triazoles by employing click chemistry. All the synthesized hybrids were characterized by FTIR, 1H-NMR, 13C-NMR spectroscopy and HRMS. These scaffolds were tested in vitro for their antifungal evaluation against different candida species. Screening against the used fungal strains, the results outcome that imidazole-indole hybrids bearing antifungals more effectively reduced than imidazole-indole-1,2,3-triazole hybrids with their MIC80 values in the range of 2–128 µg/mL. Among all the synthesized hybrids, 2a and 2b were found to be the most potent against fungal strains as a result of different methods like, time kill assays, effect on fungal membrane and antibiofilm activity. The docking simulations of the most active hybrids, 2a, 2b and 2c were carried out in the active site of sterol 14-alpha demethylase enzyme of Candida albicans. [ABSTRACT FROM AUTHOR]

The present study describes a facile and efficient synthesis of 1-(N-arylacetamide)-4-phenyl-2-pyrazolyl-imidazole 7a–7t by reacting 1-(4-phenyl-1H-imidazol-2-yl)-1H-pyrazole (3a)/3,5-dimethyl-1-(4-phenyl-1H-imidazol-2-yl)-1H-pyrazole (3b) with 2-bromo-N-substitutedacetamide 6a–6j) in good yield. The structure of compounds 7a–7t are confirmed by various spectral techniques. All the prepared compounds are examined for in-vitro antimicrobial activities against three bacterial strains; S. aureus, B. subtilis and E. coli and two fungal strains; C. albicans and A. niger. The synthesized analogues show moderate inhibitory activity against tested bacterial strains and the compounds 7a, 7b, 7l, 7m and 7r exhibited good activity against C. albicans. Most of the compounds obey the Lipinski rule of five. The compound 7b is docked in the active site of C. albicans sterol-14α-demethylase and DNA gyrase to find the binding conformation. [ABSTRACT FROM AUTHOR]

The highly substituted 1,2,4-trisubtituted imidazole was regioselectively synthesized via base mediated domino reaction of amidine scaffold with phenacyl bromide followed by in situ N-alkylation of imidazole. The reaction conditions were optimized in order to access three phenomenon (neutralization, condensation, and N-alkylation) in a single pot. A mechanism for the formation of N–H imidazole and its subsequent N-alkylation is depicted by isolation of reaction of intermediates. Electron donating group facilitate N-alkylation, whereas no N-alkylation was observed in the presence of electron withdrawing (NO2) group. The synthesized compounds and reaction intermediate were characterized using NMR, FTIR, and HRMS. Exact orientation of various aromatic rings in regioselective N-alkylated product was confirmed using single crystal X-ray analysis. [ABSTRACT FROM AUTHOR]

N-((1-substituted aryl)-1H-1,2,3-triazol-4-yl)methyl)-1H-imidazole-2-carbaldehyde analogues were synthesized in good yield from the reaction of 1-(prop-2-yn-1-yl)-1H-imidazole-2-carbaldehyde with various organic azides in the presence of Cu(I) catalyst. The structure elucidation of methylene linked imidazole-triazole compounds was achieved by various spectral methods i.e. FT-IR, 1D-NMR, 2D-NMR and MS. The newly constructed molecules were screened in-vitro against bacterial strains Bacillus subtilis, Staphylococcus epidermidis, Escherichia coli and Pseudomonas aeruginosa and fungal strains Candida albicans and Aspergillus niger. Compound 3e was most potent against E. coli and S. epidermidis and 3j was potent against all tested strains. The docking study showed that compound 3e inhibited the enzyme DNA gyrase in fruitful manner. [ABSTRACT FROM AUTHOR]

• Pyrazolyl-imidazole-triazole hybrids (3a-3r) has been designed and synthesized • The hybrids were characterized by IR, 1H, 13C NMR, HRMS and X-ray crystallography • 3c, 3d, 3e, 3m showed more than two-fold inhibitory efficacy against C. albicans • 3c showed five-fold inhibitory efficacy compared with fluconazole against A. niger • 3o interacted with E. coli topoisomerase-II DNA gyrase through hydrogen bonding A small library of novel pyrazolyl-imidazole-triazole hybrids (3a-3r) has been designed and synthesized based on hybrid pharmacophore approach using click reaction of N-propargylated pyrazolyl-imidazole (1) with several aryl azides carrying different substituents. The hybrids were characterized by different spectral techniques like IR, 1H, 13C NMR, HRMS and X-ray crystallography. ADME profile was assessed for these derivatives to get an insight on their pharmacokinetic/dynamic attributes. The synthesized hybrids were screened for antimicrobial activities against bacterial and fungal strains. Hybrid 3o and 3k demonstrated broad spectrum antibacterial activity against all tested bacterial strains except S. aureus and even better than clinically approved drug Norfloxacin. Hybrids 3c (MIC, 0.0082 µmol/mL), 3d (MIC, 0.0075 µmol/mL), 3e (MIC, 0.0077 µmol/mL) and 3m (MIC, 0.0081 µmol/mL) showed more than two-fold inhibitory efficacy against C. albicans while against A. niger, 3c (MIC, 0.0082 µmol/mL) showed five-fold inhibitory efficacy as compared with Fluconazole. Moreover, in-silico molecular docking study investigated on E. coli topoisomerase-II DNA gyrase revealed a good binding interaction with most potent hybrids 3o and 3k. [Display omitted] [ABSTRACT FROM AUTHOR]

• Regioselective synthesis of 1,4-disubstituted imidazole-pyrazole-triazole hybrids by using click chemistry. • The compound 6m demonstrated excellent potency for A. niger (MIC value 0.0064 µmol/mL) better than that of the reference drug Fluconazole (MIC value 0.0112 µmol/mL). • Molecular docking analysis of hybrid 6g in binding site of E. coli DNA gyrase was carried out. • Molecular docking analysis of hybrid 6m in binding site of C. albicans 14 alpha demthylase was carried out. A series of eighteen pyrazole-imidazole-triazole hybrid (2-(4-((2-(substituted-1H-pyrazol-1-yl)-4-phenyl-1H-imidazol-1-yl)methyl)-1H-1,2,3-triazol-1-yl)-N-(substituted)phenylacetami- de) (6a-6r) are synthesized through click reaction between in situ generated 2-azido-N-substituted acetamide and N-propargylated pyrazole-imidazole derivatives which in turn has been obtained regioselectively from 1-(1H-imidazol-2-yl)-1H-pyrazole and propargyl bromide. The structure of synthesized compounds (6a-6r) was confirmed by various spectroscopic studies (1D and 2D NMR, FT-IR, HRMS) and evaluated for antimicrobial activity. The compound 6m demonstrated excellent potency for A. niger (MIC value 0.0064 µmol/mL); even better than that of the reference drug Fluconazole (MIC value 0.0112 µmol/mL). Further, the binding conformation of most active compounds was ascertained by molecular docking studies. Image, graphical abstract [ABSTRACT FROM AUTHOR]