Design, Synthesis, Molecular Docking Studies of Deferasirox Derivatives of 1,2,4‐Triazole as Potential Antimicrobial Agents

• Published in: ChemistrySelect (Weinheim) Vol. 6; no. 45; pp. 12914 - 12920
• Main Authors: Hu, Yiping, Jiao, Shulin, Wang, Yanyan, Chen, Ruicheng, Li, Gen, Zou, Zhihong
• Format: Journal Article
• Language: English
• Published: 06-12-2021
• Subjects: 1,2,4-Triazole; Antifungal agents; Biological activity; Molecular docking; Synthesis design
• ISSN: 2365-6549; 2365-6549
• DOI: 10.1002/slct.202103955

A series of deferasirox derivatives of 1,2,4‐triazole (5 a–i,6 a–g) were designed and synthesized by the ring‐opening rearrangement reaction of phenyl hydrazine or its substituents and imines, compounds 5 d–i, 6 e–g are previously unknown. Obtained derivatives were characterized by IR, 1H NMR, 13C NMR, and Mass spectral. The antibacterial activities of all compounds against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Candida albicans and Aspergillus niger were experimentally evaluated. Most of them exhibited potential antimicrobial activity and promising antifungal activity. Especially, 6 f and 6 g showed the best antimicrobial activity (MIC90=0.125–2.0 μg/mL) against Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli, while compounds 6 c, 6 e showed excellent antifungal activity (MIC90=0.5–2.0 μg/mL). The molecular docking analysis further revealed that all the synthesized derivatives have shown potential binding affinities.
Imine intermediates are synthesized from substituted salicylic acid and salicylic amide and then condensed with phenyl‐hydrazine derivatives to obtain a series of 3, 5‐bis (2‐hydroxyphenyl) −1‐phenyl‐1, 2, 4 triazoles derivatives. All compounds were evaluated for antimicrobial activity and some of the compounds were found to have potential drug activity. The binding mode of compounds and microbial protein was further explained by molecular docking technology.