New Quinazolinone‐Tethered 1,2,3‐Triazoles aSs Potent Antimicrobial Agents: Design, Synthesis, Biological Evaluation and in silico Docking Study

• Published in: ChemistrySelect (Weinheim) 2024-08, Vol.9 (30), p.n/a
• Main Authors: Patel, Jeevan Lal, Sureddy, Naveen Kumar, Chedupaka, Raju, Papisetti, Venkatesham, Mahapatra, S. P., Penta, Santhosh
• Format: Article
• Language: English
• Subjects: 1,2,3-triazole; 1A19; ADMET properties; Antimicrobial agents; Docking interactions; Quinazolinone
• ISSN: 2365-6549; 2365-6549
• DOI: 10.1002/slct.202400876

Novel 1,2,3‐triazole acetamide linked quinazolinone derivatives were synthesized via click reaction, by reacting of 3‐methyl‐2‐(prop‐2‐yn‐1‐ylthio)quinazolin‐4(3H)‐one with various aryl azides as prominent fungal pathogen Candida albicans interactions. The prepared triazole compounds were characterized using mass spectrometry, 1H NMR, 13C NMR, and IR spectroscopic techniques. Compounds were screened for their in vitro antibacterial and antifungal activity against a variety of microorganisms namely, Bacillus subtilis, Enterococcus faecalis, Klebsiella pneumonia, Escherichia coli, Aspergillus fumigatus, Candida albicans, and Aspergillus clavatus. Quinazolinone linked p‐hydroxyphenyl, o, p‐dihydroxyphenyl and o‐dimethylamino phenyl triazoles showed a remarkable antibacterial activity against E. faecalis with MIC values of 3.20±0.01, 4.01±0.04, and 4.10±0.01 μg mL−1, and screened compounds p‐nitrophenyl substituted triazole, and p‐methylphenyl substituted triazole displayed a significant antifungal activity against C. albicans with MICs of 3.16±0.01, 4.06±0.03 μg mL−1, compared to itraconazole (MIC=3.32±0.02 μg mL−1). For further exploration of the anti‐fungal mechanism of action, molecular docking was carried out for these compounds in C. albicans active site as one of the important antifungal inhibitors (PDB: 1A19). Furthermore, the ADMET profile was evaluated for all the final triazole compounds in contrast to reference drugs moxifloxacin and itraconazole. In conclusion, we discovered a novel quinazolinone linked 1,2,3‐triazoles with promising antimicrobial activity and a favorable pharmacokinetic profile. Scheme: Synthesis of quinazolinone with 1,2,3‐triazole moieties and their 2D structure and Ligplot docking interactions Scheme: Synthesis of quinazolinone with 1,2,3‐triazole moieties.