{
  "abstract": "Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disorder with multifactorial pathogenesis. Amyloid beta (Aβ) and monoamine oxidase (MAO) are among the key therapeutic targets for its treatment. In this investigation, a series of 18 new naphthalimide-based derivatives were synthesized and assessed for multitarget activity against hAChE, esBuChE, MAO-A, MAO-B, Aβ, and paired helical fragment 6 (PHF6) aggregation. The screened compounds predominantly exhibited dual inhibition of MAO-B and Aβ aggregation to counteract oxidative stress and plaque formation. Among the tested compounds, P12 and P17 were found to have remarkable inhibition against Aβ, with 83% and 91% inhibition, respectively, compared to the reference compound quercetin (75% inhibition). The compound P10 was the most effective MAO-B inhibitor, with an IC₅₀ value of 3.09 ± 0.10 µM. Cytotoxicity studies in SH-SY5Y cells confirmed that compounds were non-toxic up to 25 µM. Additionally, the neuroprotection assays revealed that P10 was capable of reducing oxidative stress effectively against H₂O₂-induced toxicity, while P12 showed superior protection against Aβ-induced neurotoxicity in SH-SY5Y cells. Furthermore, in silico investigations provided structural insights into the predicted ligand-target interaction modes and dynamic behavior of the selected compounds with MAO-B and monomeric Aβ1-42. Consequently, all these findings underscore that naphthalimide derivatives are promising dual inhibitors of amyloid-β aggregation and MAO-B and have potential for further development as MTDLs for AD.",
  "abstract_shown": true,
  "affiliations": [
    "Drug Design and Synthesis Lab., Department of Chemistry, Jamia Millia Islamia New Delhi-110025 India nhoda@jmi.ac.in +0091-11-26985507 +0091-9910200655.",
    "Department of Pharmacy-Pharmaceutical Sciences, University of Bari Aldo Moro Via E. Orabona 4 70125 Bari Italy marco.catto@uniba.it.",
    "Department of Medicine and Surgery, LUM University Giuseppe Degennaro Torre Rossi 70010 Casamassima Italy.",
    "Department of Molecular Medicine, Jamia Hamdard New Delhi 110062 India."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Rukshar Praveen"
    },
    {
      "affs": [
        1
      ],
      "name": "Alessandro Gadaleta"
    },
    {
      "affs": [
        1
      ],
      "name": "Gabriella La Spada"
    },
    {
      "affs": [
        2
      ],
      "name": "Daniela Valeria Miniero"
    },
    {
      "affs": [
        3
      ],
      "name": "Aquib Reza"
    },
    {
      "affs": [
        0
      ],
      "name": "Tohasib Yusub Chaudhari"
    },
    {
      "affs": [
        0
      ],
      "name": "Abdur Rahman"
    },
    {
      "affs": [
        1
      ],
      "name": "Marco Catto",
      "orcid": "0000-0002-8411-304X"
    },
    {
      "affs": [
        0
      ],
      "name": "Nasimul Hoda",
      "orcid": "0000-0001-9779-2056"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/39s5r4m59qqrv.bib",
  "cited_by": 0,
  "doi": "10.1039/d6ra07131g",
  "fulltext_url": "https://europepmc.org/articles/PMC13639867",
  "id": "39s5r4m59qqrv",
  "issns": [
    "2046-2069"
  ],
  "landing_url": "https://europepmc.org/article/MED/42840889",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2736|Cholinesterase and Neurodegenerative Diseases"
    ]
  ],
  "openalex": "W7220720388",
  "pdf_url": "https://europepmc.org/articles/PMC13639867?pdf=render",
  "pmcid": "PMC13639867",
  "pmid": "42840889",
  "published": "2026-10-06",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/39s5r4m59qqrv.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:10Z",
      "native_id": "MED:42840889",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42840889"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2736|Cholinesterase and Neurodegenerative Diseases",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Design, synthesis, and biological evaluation of naphthalimide derivatives as dual monoamine oxidase-B and amyloid-β aggregation inhibitors for Alzheimer's disease.",
  "title_text": "Design, synthesis, and biological evaluation of naphthalimide derivatives as dual monoamine oxidase-B and amyloid-β aggregation inhibitors for Alzheimer's disease.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:10Z",
  "url": "https://research.draconitic.com/paper/39s5r4m59qqrv",
  "venue": "RSC advances",
  "versions": []
}