Novel Etodolac-Based 1,2,4-Triazole Derivatives as Antimicrobial Agents: Synthesis, Biological Evaluation, and Molecular Docking Study

• Published in: Russian journal of organic chemistry Vol. 56; no. 12; pp. 2179 - 2187
• Main Authors: Shaik, A., Rao, A. T., Venkatarao, D. V., Rao, S. V. M. Mohan, Kishore, P. V. V. N.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 01.12.2020; Springer Nature; Springer Nature B.V
• Subjects: Antioxidants; Ascorbic acid; Bonding strength; Chemical synthesis; Chemistry; Chemistry and Materials Science; Chemistry, Organic; Enterobacter cloacae; Glycogens; Hydrogen bonding; Kinases; Klebsiella; Mass spectra; Microorganisms; Molecular docking; NMR; Nonsteroidal anti-inflammatory drugs; Nuclear magnetic resonance; Organic Chemistry; Physical Sciences; Pseudomonas aeruginosa; Science & Technology; Streptococcus infections; Triazoles; nonsteroidal anti-inflammatory drugs; antibacterial activity; docking studies; GSK-3; 1,2,4-triazoles; antioxidant activity; 1; 2; 4-triazoles
• ISSN: 1070-4280; 1608-3393
• DOI: 10.1134/S1070428020120210

A series of novel 1,2,4-triazole nonsteroidal anti-inflammatory drugs (NSAIDs) derived from etodolac were designed and synthesized. The synthesized compounds were identified using 1 H and 13 C NMR, IR, and mass spectra and elemental analyses and evaluated for their in vitro antibacterial activity against Gram-positive microorganisms like Streptococcus pneumoniae and Klebsiella pneumoniae and Gram-negative strains such as Pseudomonas aeruginosa and Enterobacter cloacae with pefloxacin as a reference drug. Some compounds showed a potent activity at a concentration 50 mg/mL with inhibition zones of 30 to 36 mm against S. pneumoniae . Etodolac-derived N -isobutyl- and N -ethyl-1,2,4-triazoles containing 4-methoxybenzylsulfanyl and 3-nitrobenzylsulfanyl groups were active against P. aeruginosa with inhibition zones of 25–29 mm at a concentration of 50 mg/mL. All compounds showed excellent antioxidant activity with IC 50 values ranging from 72.39±0.25 µg/mL to 16.39±0.65 µg/mL in comparison with ascorbic acid (IC 50 16.81±0.18 µg/mL). Molecular docking studies revealed strong hydrogen bonding, π–π, and π–σ interactions of 3-nitro-, 4-methoxy-, and 4-methylbenzyl moieties with Ser421, Val120, Tyr124, Phe319, Ala44, and Val120 amino acid residues of the active site of glycogen synthase kinase-3 (GSK-3) protein.