{
  "abstract": "The hybridization approach was employed to design a single pharmacophore based on the conjugation of paracetamol with thiazole derivatives, yielding thiazole-paracetamol hybrid derivatives 4-11 that utilize a linker from hydrazone (-C[double bond, length as m-dash]N-NH) and azo (-N[double bond, length as m-dash]N-) linkers, serving as the hydrogen bond donor/acceptor binding site. The structure of the designed derivatives was fully characterized and confirmed using analytical data (IR, ¹H NMR, and ¹³C NMR), and elemental analysis. The anti-inflammatory potential of the synthesized hybrids was evaluated using in vitro COX-2 enzymatic inhibition assay. The compounds exhibited moderate to excellent COX-2 inhibitory activity, with IC₅₀ values ranging from 0.81 to 7.27 µM, compared with celecoxib (IC₅₀ = 0.62 ± 0.02 µM). Among the synthesized derivatives, the 5-acetyl-4-methylthiazole candidate 8 emerged as the most potent inhibitor, displaying an IC₅₀ value of 0.81 ± 0.02 µM, whereas the 5-ethoxycarbonyl-4-methylthiazole derivative 7 also demonstrated pronounced activity (IC₅₀ = 1.35 ± 0.15 µM). The SAR analysis revealed that the 4-methylthiazole scaffold was more favorable for COX-2 inhibition than the corresponding 4-oxo-4,5-dihydrothiazole scaffold, while the introduction of compact carbonyl-containing substituents at the C-5 position markedly enhanced inhibitory potency. In contrast, aromatic substitution or incorporation of a 4-oxo-4,5-dihydrothiazole ring reduced activity. Furthermore, compounds 7 and 8 exhibited low-micromolar COX-1 inhibitory activity (IC₅₀ = 0.89 ± 0.05 and 0.72 ± 0.02 µM, respectively), demonstrating dual activity toward COX-1/2 inhibition. In addition, compound 8 effectively suppressed the production of TNF-α and IL-6, with IC₅₀ values of 1.48 ± 0.50 and 1.80 ± 0.35 µM, respectively, showing inhibitory activity comparable to that of celecoxib (IC₅₀ = 1.40 ± 0.10 and 1.74 ± 0.20 µM, respectively). The docking process of the most promising derivative 8 demonstrated strong binding affinity and various types of interactions, including hydrogen bonding, π-π stacking, and hydrophobic interactions (π-alkyl and alkyl). In addition, ADMET prediction indicated a favorable pharmacokinetic profile and acceptable toxicity levels. These findings identify compound 8 as a promising lead candidate for the development of next-generation anti-inflammatory agents with dual cyclooxygenase inhibitory and immunomodulatory properties.",
  "abstract_shown": true,
  "affiliations": [
    "Health Specialties, Basic Sciences and Their Applications Unit, Applied College, Muhayl Asir, King Khalid University Abha 62529 Saudi Arabia.",
    "Department of Chemistry, Faculty of Science (Girls), Al-Azhar University Nasr City Cairo Egypt.",
    "Department of Chemistry, Faculty of Science (boys), Al-Azhar University 11884 Nasr City Cairo Egypt Ahmed_ragab@azhar.edu.eg ahmed_ragab7@ymail.com.",
    "Polymer Institute, Slovak Academy of Sciences SAS Dúbravská cesta 9 845 41 Bratislava Slovakia.",
    "Center for Scientific Research and Entrepreneurship, Northern Border University Arar 73213 Saudi Arabia Mohammed.Hlal@nbu.edu.sa.",
    "Chemistry Department, Faculty of Science, Galala University Galala City Suez 43511 Egypt ahmed.abdelwahab@gu.edu.eg."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Mohamed A Salem"
    },
    {
      "affs": [
        1
      ],
      "name": "Radwa Ayman"
    },
    {
      "affs": [
        2
      ],
      "name": "Yousry A Ammar",
      "orcid": "0000-0001-8989-4394"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Moustafa S Abusaif",
      "orcid": "0000-0002-1084-3904"
    },
    {
      "affs": [
        4
      ],
      "name": "Mohamed H Helal",
      "orcid": "0000-0002-3769-4670"
    },
    {
      "affs": [
        2,
        5
      ],
      "name": "Ahmed Ragab",
      "orcid": "0000-0001-8542-7465"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9b2aeqd9jqy8p.bib",
  "cited_by": 0,
  "doi": "10.1039/d6ra07351d",
  "fulltext_url": "https://europepmc.org/articles/PMC13692719",
  "id": "9b2aeqd9jqy8p",
  "issns": [
    "2046-2069"
  ],
  "landing_url": "https://europepmc.org/article/MED/42921339",
  "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",
      "1605|Synthesis and biological activity"
    ]
  ],
  "openalex": "W7223258869",
  "pdf_url": "https://europepmc.org/articles/PMC13692719?pdf=render",
  "pmcid": "PMC13692719",
  "pmid": "42921339",
  "published": "2026-10-23",
  "publisher": "Royal Society of Chemistry",
  "ris": "https://research.draconitic.com/paper/9b2aeqd9jqy8p.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:33Z",
      "native_id": "MED:42921339",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42921339"
    },
    {
      "first_seen": "2026-11-07T12:23:47Z",
      "native_id": "PMC13692719",
      "source": "pmc",
      "url": "https://doi.org/10.1039/d6ra07351d"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1605|Synthesis and biological activity",
      "subfield": "organic"
    }
  ],
  "title": "Innovative design and development of novel thiazole-paracetamol hybrids as COX inhibitors and immunomodulatory activity: design, synthesis, SAR, in vitro biological evaluation, and molecular docking analysis.",
  "title_text": "Innovative design and development of novel thiazole-paracetamol hybrids as COX inhibitors and immunomodulatory activity: design, synthesis, SAR, in vitro biological evaluation, and molecular docking analysis.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:21:07Z",
  "url": "https://research.draconitic.com/paper/9b2aeqd9jqy8p",
  "venue": "RSC advances",
  "versions": []
}