ABSTRACT
Some urea-thiazole/benzothiazole hybrids with a triazole linker were synthesized via Cu(I)-catalysed click reaction. After successfully analysed by various spectral techniques including FTIR, NMR and HRMS, antimicrobial screening of the synthesized hybrids along with their precursors was carried out against two Gram (+) bacteria (Staphylococcus aureus and Bacillus endophyticus), two Gram (-) bacteria (Escherichia coli and Pseudomonas fluorescens) and two fungi (Candida albicans and Rhizopus oryzae). All the synthesized compounds (4a-4l) displayed better biological response than the standard fluconazole against both of the tested fungi. Compounds 4h and 4j were found to be the most active compounds against R. oryzae and C. albicans, respectively. Molecular docking of hybrid 4j and its alkyne precursor 1b in the active site of C. albicans target sterol 14-α demethylase was also performed and was also supported by molecular dynamics studies. In silico ADME prediction of synthesized urea-thiazole/benzothiazole hybrids with a triazole linker and their alkyne precursors was also predicted.
Subject(s)
Anti-Infective Agents , Triazoles , Alkynes/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Benzothiazoles/pharmacology , Candida albicans , Escherichia coli , Fluconazole , Microbial Sensitivity Tests , Molecular Docking Simulation , Molecular Structure , Sterols , Structure-Activity Relationship , Triazoles/chemistry , Triazoles/pharmacology , Urea/pharmacologyABSTRACT
The need to overcome ever-increasing cases of antifungal resistance and circumvent side effects and drug interactions related to currently available drugs has impelled the demand to expedite the drug discovery and the development of novel antifungals. 1,4-disubstituted 1,2,3-triazole has gained tremendous interest in the last two decades mainly because of its ease of synthesis via copper( I)-catalyzed azide-alkyne cycloaddition (CuAAC) and its broad spectrum of chemotherapeutic potential. 1,2,3-Triazole is an excellent pharmacophore that has been used as a bioisostere for obtaining libraries of new medicinally important scaffolds. The present review focuses on the recent advances (2016-2021) in 1,2,3-triazole derivatives obtained by CuAAC as potential antifungal agents that may facilitate the triazole-based antifungal development process.
