Antimicrobial and antibiofilm activity of substituted pyrazoles: Design, synthesis and molecular docking studies
Journal of Molecular Structure, cilt.1359, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 1359
- Basım Tarihi: 2026
- Doi Numarası: 10.1016/j.molstruc.2026.145436
- Dergi Adı: Journal of Molecular Structure
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, Chimica, Compendex, INSPEC, Academic Search Ultimate (EBSCO), Engineering Source (EBSCO)
- Anahtar Kelimeler: Pyrazole, Multicomponent reactions, Sonochemistry, Antimicrobial activity, Antibiofilm activity, Antioxidant activity, Molecular docking
- Kırklareli Üniversitesi Adresli: Evet
Özet
A series of novel 5-amino-4-cyano-N-aroylpyrazoles was synthesized in a simple and environmentally friendly process in the presence of (±)-10-camphorsulfonic acid (CSA) catalyst in aqueous medium through the treatment of aromatic aldehydes with malononitrile and benzhydrazide or 4-hydroxybenzhydrazide under ultrasonic irradiation. The synthesized compounds were evaluated for their antioxidant, antimicrobial and antibiofilm activities. Compounds 5n, 5i, 5f, 5k, 5m, 5a, 4m, 5g, 4i, 4k and 4n exhibited the highest antioxidant activity with 91,45%, 89,52%, 88,70%, 88,10%, 84,47%, 83,70%, 80,45%, 79,57%, 77,20%, 76,35%, and 75,24%, respectively. Antimicrobial activity evaluation was made against the bacterial strains: S. aureus (ATCC 25,923), and Escherichia coli(ATCC 25,922). Compounds 4f, 4g, 4j, 4l, 4n, 5a, 5b, 5d, 5e, 5g, 5j, 5l, 5m, and 5n exhibited promising antibacterial activity against S. aureus with 0,0625, 0,0156, 0,0625, 0,0625, 0,0312, 0,0625, 0,0625, 0125, 0125, 0,0156, 0,0312, 0,0625, 0,0312, and 0125 mM, respectively, while compounds 4f, 4g, 4h, 4k, 4l, 4n, 5d, 5e, 5l, 5m and 5n exhibited significant activity against E. coliwith 0,0312, 0,0156, 0125, 0125, 0,0156, 0125, 0125, 0125, 0,0156, 0,0312, and 0125 mM, respectively. Biofilm inhibition results indicated that some of the synthesized compounds were highly active. Compounds 4g, 4j, 4n, 5g, 5j, 5l, 5m, and 5n inhibited S. aureus (ATCC 25,923) biofilm by 66%-88%, while compounds 4g, 4f, 4m and 5n inhibited E. coli(ATCC 25,922) biofilm by 67%-73%. Synthesized compounds were also scrutinized using DFT-B3LYP basis set. Additionally, a comprehensive investigation into the ADME (Absorption, Distribution, Metabolism, and Excretion) properties of these compounds was conducted. Docking simulations were performed using two structurally distinct DNA gyrase: the GyrB ATPase domain (PDB: 1KZN) and the DNA-bound GyrA interface complex (PDB: 2XCS), also the efflux protein NorA (PDB: 4DX5) was used, to elucidate potential binding interactions and to predict their role in antimicrobial mechanisms. Compounds 4l, 4n, 5l, and 5n exhibited notable activity. In particular, compound 4n exhibited the highest binding affinity with all selected targets, in the range -9.88 to -6.11 kcal/mol, demonstrating its potential as an effective antimicrobial agent. Molecular docking studies on the antimicrobial activity of the synthesized compounds were correlated with the experimental results.