{
  "abstract": "Diabetes mellitus is a major global health concern that demands robust therapeutic strategies to control postprandial hyperglycemia. In this study, a new series of 3D-spirochroman–cycloalkane hybrids bearing nitrogen-containing moieties, including azines, hydrazides, hydrazones, pyrazoles, and pyrroles were rationally designed and effectively synthesized in moderate to excellent yields. Upon evaluation as dual inhibitors of α -amylase and α -glucosidase enzymes, several compounds surpassed the benchmark drug acarbose (IC ₅₀ = 78.9 and 43.3 µM, respectively). Nicotinonitrile 6 showed the strongest α -amylase inhibition (IC ₅₀ = 21.3 µM), while hydrazone 15 exhibited the highest α -glucosidase inhibition potency (IC ₅₀ = 18.2 µM). Hydrazone 12a displayed the most balanced dual inhibitory profile (IC ₅₀ = 25.3 and 29.1 µM). Cytotoxicity assessments of compounds 6 , 12a , and 15 on Vero and WI-38 cell lines revealed minimal inhibitory effects on cell viability (IC ₅₀ ≈ 316.15–611.52 µM). Molecular docking studies highlighted a favourable binding within enzyme active sites stabilized by hydrogen-bonding and hydrophobic interactions, and ADMET predictions indicated improved drug-likeness, gastrointestinal absorption, and high bioavailability of compounds 6 , 12a , and 15 compared with acarbose. DFT calculations showed that the nitrogen substitution modulates molecular orbital energies and reduces HOMO–LUMO gaps, serving as descriptors of electronic structure, while complementary multi-wave function analyses (ESP, NCI, and ELF) revealed charge redistribution and enhanced noncovalent interaction patterns consistent with the observed activity and selectivity.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "name": "Y. E. Bakr"
    },
    {
      "name": "M. A. Abozeid"
    },
    {
      "name": "M. M. Abou-Elzahab"
    },
    {
      "name": "S. U. Khan"
    },
    {
      "name": "F. H. Elghareeb"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6kxc3ywazr0n2.bib",
  "cited_by": 0,
  "doi": "10.1038/s41598-026-74462-y",
  "fulltext_url": null,
  "id": "6kxc3ywazr0n2",
  "issns": [
    "2045-2322"
  ],
  "landing_url": "https://www.nature.com/articles/s41598-026-74462-y",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0",
  "metadata_licence": null,
  "native_subjects": [],
  "openalex": null,
  "pdf_url": "https://www.nature.com/articles/s41598-026-74462-y.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-05",
  "publisher": "Springer Science and Business Media LLC",
  "ris": "https://research.draconitic.com/paper/6kxc3ywazr0n2.ris",
  "sources": [
    {
      "first_seen": "2026-11-05T12:20:13Z",
      "native_id": "10.1038/s41598-026-74462-y",
      "source": "crossref",
      "url": "https://www.nature.com/articles/s41598-026-74462-y"
    }
  ],
  "subjects": [],
  "title": "Nitrogen-functionalized rigid 3D-spirochroman–cycloalkane hybrids as dual α-amylase and α-glucosidase inhibitors: synthesis, biological evaluation, and computational insights",
  "title_text": "Nitrogen-functionalized rigid 3D-spirochroman–cycloalkane hybrids as dual α-amylase and α-glucosidase inhibitors: synthesis, biological evaluation, and computational insights",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T00:20:49Z",
  "url": "https://research.draconitic.com/paper/6kxc3ywazr0n2",
  "venue": "Scientific Reports",
  "versions": []
}