{
  "abstract": "The emergence of multidrug-resistant bacterial pathogens and biofilm-associated infections highlights the urgent need for antibacterial agents with novel chemical architectures and complementary modes of action. In the present study, a new series of diphenylpyrazole-based hydrazine-1-carboximidamide derivatives (5a–i) was designed, synthesized, and evaluated as potential antibacterial and antibiofilm agents. The target compounds were obtained through a three-step synthetic sequence involving phenylhydrazone formation, Vilsmeier–Haack cyclization/formylation, and subsequent condensation with aminoguanidine bicarbonate. Structural characterization was established using spectroscopic and mass spectrometric techniques. The synthesized derivatives exhibited variable antibacterial activity against representative Gram-positive and Gram-negative bacteria, demonstrating a pronounced structure-dependent response. Among the series, compound 5g bearing a nitrophenyl substituent emerged as the most promising derivative, displaying MIC values of 8, 4, 4, and 16 µg mL−1 against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa, respectively. Compound 5g also showed substantial antibiofilm activity at 0.5 × MIC, with inhibition values of 75.95%, 53.33%, 77.57%, and 63.73% against the corresponding bacterial strains. Time-kill studies demonstrated a concentration- and time-dependent bactericidal effect against E. coli ATCC 25922, while potassium leakage and scanning electron microscopy provided complementary evidence of bacterial membrane perturbation and cellular-envelope damage. Furthermore, compound 5g exhibited promising anti-quorum-sensing activity against P. aeruginosa, significantly reducing pyocyanin production by 26.80% and 54.33% at ¼ and ½ MICs, respectively. Importantly, 5g exhibited low cytotoxicity toward WI-38 normal human cells (IC50 = 255 ± 22.1 µg mL−1) and a favorable selectivity index of 32. Collectively, these findings identify diphenylpyrazole carboximidamide 5g as a promising multifunctional antibacterial lead with direct antibacterial, antibiofilm, membrane-perturbing, and anti-quorum-sensing activities, warranting further optimization and mechanistic investigation.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University Madinah Saudi Arabia",
    "Department of Pharmacognosy and Pharmaceutical Chemistry, College of Pharmacy, Taibah University Madinah Saudi Arabia",
    "Medical Laboratory Sciences, Fakeeh College for Medical Sciences, Fakeeh Care Group Jeddah 21461 Saudi Arabia",
    "Pharmacy Student, College of Pharmacy, Taibah University Madinah 41477 Saudi Arabia",
    "Pharmaceutical Science Department, College of Pharmacy, King Saud bin Abdulaziz University for Health Science Riyadh Saudi Arabia",
    "Department of Chemistry, Faculty of Science, Islamic University of Madinah Madinah 42351 Saudi Arabia",
    "Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University Sakaka 72388 Saudi Arabia",
    "Department of Pharmacognosy, College of Pharmacy, Jouf University Sakaka Aljouf 72388 Saudi Arabia",
    "Microbiology and Immunology Department, Faculty of Pharmacy, Al-Azhar University Nasr City 11884 Cairo Egypt",
    "Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Al-Azhar University Cairo 11884 Egypt"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Sara A. Almadani"
    },
    {
      "affs": [
        1
      ],
      "name": "Ahmed K. B. Aljohani",
      "orcid": "0000-0003-2332-1125"
    },
    {
      "affs": [
        0
      ],
      "name": "Bandar D. Alrehaili"
    },
    {
      "affs": [
        2
      ],
      "name": "Safaa A. Turkistani"
    },
    {
      "affs": [
        3
      ],
      "name": "Shahad N. Almuzani"
    },
    {
      "affs": [
        3
      ],
      "name": "Maysa M. Aljuhani"
    },
    {
      "affs": [
        3
      ],
      "name": "Ghada Y. Alsayed"
    },
    {
      "affs": [
        3
      ],
      "name": "Ruba A. Alharbi"
    },
    {
      "affs": [
        4
      ],
      "name": "Hadeel Z. Alraddadi"
    },
    {
      "affs": [
        5
      ],
      "name": "Sobhi M. Gomha",
      "orcid": "0000-0002-7739-2837"
    },
    {
      "affs": [
        6
      ],
      "name": "Mohamed A. Abdelgawad"
    },
    {
      "affs": [
        7
      ],
      "name": "Arafa Musa",
      "orcid": "0000-0003-0979-556X"
    },
    {
      "affs": [
        1
      ],
      "name": "Raed Alghamdi",
      "orcid": "0009-0003-3016-3142"
    },
    {
      "affs": [
        8
      ],
      "name": "Mohammed S. Abdulrahman"
    },
    {
      "affs": [
        9
      ],
      "name": "Hany E. A. Ahmed",
      "orcid": "0000-0001-8898-8452"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/crtm79a6jt4hs.bib",
  "cited_by": 0,
  "doi": "10.1039/d6ra08952f",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13720906/?tool=EBI",
  "id": "crtm79a6jt4hs",
  "issns": [
    "2046-2069"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13720906",
  "language": "eng",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Chemistry"
    ],
    [
      "openalex",
      "1312|Bacterial biofilms and quorum sensing"
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  "openalex": "W7224783984",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13720906/pdf/?tool=EBI",
  "pmcid": "PMC13720906",
  "pmid": "42964978",
  "published": "2026-10-30",
  "publisher": "Royal Society of Chemistry",
  "ris": "https://research.draconitic.com/paper/crtm79a6jt4hs.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:21:36Z",
      "native_id": "PMC:PMC13720906",
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    },
    {
      "first_seen": "2026-11-03T12:21:42Z",
      "native_id": "PMC13720906",
      "source": "pmc",
      "url": "https://doi.org/10.1039/d6ra08952f"
    }
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  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Bacterial biofilms and quorum sensing",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Synthesis, characterization, and evaluation of novel diphenylpyrazole-based hydrazine-1-carboximidamides as broad-spectrum antibacterial leads with antibiofilm and virulence-modulating activities",
  "title_text": "Synthesis, characterization, and evaluation of novel diphenylpyrazole-based hydrazine-1-carboximidamides as broad-spectrum antibacterial leads with antibiofilm and virulence-modulating activities",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:21:42Z",
  "url": "https://research.draconitic.com/paper/crtm79a6jt4hs",
  "venue": "RSC advances",
  "versions": []
}