Design, synthesis and biological evaluation of novel substituted indazole-1,2,3-triazolyl-1,3,4-oxadiazoles: Antimicrobial activity evaluation and docking study

• Published in: Results in Chemistry 2022-01, Vol.4, p.100605, Article 100605
• Main Authors: Dunga, Ananda Kumar, Allaka, Tejeswara Rao, Kethavarapu, Yugandhar, Nechipadappu, Sunil Kumar, Pothana, Pradeep, Ravada, Kishore, Kashanna, Jajula, Kishore, Pilli V.V.N.
• Format: Article
• Language: English
• Subjects: 1,2,3-Triazoles; 1,3,4-Oxadiazoles; 2ZCS; Antibacterial activity; Antifungal activity; Indazole
• ISSN: 2211-7156; 2211-7156
• DOI: 10.1016/j.rechem.2022.100605

[Display omitted] •A library of indazole derivatives have synthesized and characterized by spectroscopic techniques.•All the novel synthesized compounds were screened for their antimicrobial activities.•All designed scaffolds are displayed promising antimicrobial activity.•Molecular modeling of prepared ligands into active site of S. aureus with 2ZCS. A novel series of dual 1,2,3-triazole and 1,3,4-oxadiazole heterocyclic compounds linked to indazole were designed and efficiently synthesized using 3-bromo-1H-indazole as potential antimicrobial agents. All the compounds were characterized by their proton, carbon nuclear magnetic resonance, infrared, mass spectral data, and elemental analysis. The final compounds 9a–m were evaluated in vitro antimicrobial activity against Gram-negative microorganism E. coli, Gram-positive microorganisms B. subtilis, S. pneumoniae, S. aureus and antifungal strains A. fumigates, C. albicans. From biological screening, we were surprised to find that most of the compounds have significant inhibitory activity and in particular dual heterocycles 9b, 9c, 9h, 9i, and 9j showed outstanding antibacterial activity against Gram-positive bacteria S. pneumoniae with MICs 5.4 ± 0.02, 5.8 ± 0.03, 8.0 ± 0.04, 4.0 ± 0.03, and 7.8 ± 0.01 µg/mL respectively, when compared to ampicillin [MIC = 9.1 ± 0.01 µg/mL]. Final prepared scaffolds 9b, 9h acquiring highest potential drug scores ΔG = −7.78, −8.34 kcal/mol with their amino acids residues Arg171 (O…H: 1.934), Lys20 (N…H: 1.951), Arg265 (N…H: 2.080), ArgA:171 (2.740), ArgA:265 (1.874), TyrA:248 (1.973), and Ser19 (H…O: 2.048), Tyr248 (O…H: 1.570), Arg265 (N…H: 1.976), Arg46 (N…H: 1.059) ArgA:45 (O…H, 2.94 Å) respectively.