Scholarlink

<p>The emergence of antimicrobial resistance needs the development of new chemotherapeutic scaffolds. Pyrazole derivatives are recognized for their broad biological activity; however, further structural innovation is required to enhance antimicrobial efficacy and safety. Thus, new pyrazole-based candidates were designed and synthesized using 3-(4-chlorophenyl)-1-phenylpyrazol-4-yl-2-cyanoacryloyl chloride as a versatile precursor. A series of mono- and bidentate nucleophile-derived compounds was prepared and evaluated for antimicrobial activity against Gram-positive and Gram-negative bacteria and <i>Candida albicans</i>. Several derivatives exhibited potent antibacterial and antifungal activity, particularly against Gram-positive strains, with minimum inhibitory concentrations comparable to standard drugs. Most compounds showed low cytotoxicity toward HepG2 cells, which was further reduced upon antioxidant co-treatment. Notably, vitamin C and <i>N</i>-acetylcysteine showed synergistic enhancement of antimicrobial and antibiofilm effects. Molecular docking studies against dihydropteroate synthase (DHPS, PDB: 5U0V) revealed favorable binding interactions, with the thiophene-based derivative <b>10</b> displaying ligand efficiency comparable to the co-crystallized ligand 7VJ. Overall, these findings highlight pyrazole-based scaffolds as promising antimicrobial candidates with favorable biological profiles, providing a strong basis for further structural optimization.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Design, synthesis, biological assessment, and integrated computational analysis of new pyrazole-based antimicrobial candidates

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月10日

查看全文
  • Eman A. E. El-Helw,
  • Selwan Hamed,
  • Ahmed K. El-Ziaty,
  • Abdullah Y. A. Alzahrani,
  • Sayed K. Ramadan

摘要

The emergence of antimicrobial resistance needs the development of new chemotherapeutic scaffolds. Pyrazole derivatives are recognized for their broad biological activity; however, further structural innovation is required to enhance antimicrobial efficacy and safety. Thus, new pyrazole-based candidates were designed and synthesized using 3-(4-chlorophenyl)-1-phenylpyrazol-4-yl-2-cyanoacryloyl chloride as a versatile precursor. A series of mono- and bidentate nucleophile-derived compounds was prepared and evaluated for antimicrobial activity against Gram-positive and Gram-negative bacteria and Candida albicans. Several derivatives exhibited potent antibacterial and antifungal activity, particularly against Gram-positive strains, with minimum inhibitory concentrations comparable to standard drugs. Most compounds showed low cytotoxicity toward HepG2 cells, which was further reduced upon antioxidant co-treatment. Notably, vitamin C and N-acetylcysteine showed synergistic enhancement of antimicrobial and antibiofilm effects. Molecular docking studies against dihydropteroate synthase (DHPS, PDB: 5U0V) revealed favorable binding interactions, with the thiophene-based derivative 10 displaying ligand efficiency comparable to the co-crystallized ligand 7VJ. Overall, these findings highlight pyrazole-based scaffolds as promising antimicrobial candidates with favorable biological profiles, providing a strong basis for further structural optimization.