{
  "abstract": "Multidrug resistance (MDR) mediated by P-glycoprotein (P-gp, ABCB1) remains a major obstacle to successful chemotherapy, underscoring the need for potent and safe agents capable of blocking P-gp function and restoring drug sensitivity. To address this challenge, we synthesized and systematically evaluated a library of novel artemisinin derivatives. Screening identified compounds A7, A12, A13, A14 and A15 as effective molecules, significantly reducing rhodamine 123 (Rho123) efflux at minimum effective concentrations (MECs) ranging from 0.19 to 6 µM. Notably, compounds A16 and A20 displayed the highest potency, with MECs as low as 0.049 µM. These derivatives also efficiently inhibited P-gp-mediated doxorubicin (Dox) efflux, with a MEC value of 0.19 µM for compound A16 and 0.049 µM for compound A20. Consistent with these findings, both compounds markedly enhanced Dox cytotoxicity by sensitizing K562/Dox cells at concentrations of 0.050 and 0.005 µM, respectively. Molecular dynamics simulations and multiscale QM/MM calculations yielded useful clues for understanding the binding modes of the derivatives and identified key structural determinants and key amino acid residues that would be involved in P-gp modulation. The potent P-gp-modulating activity of compounds A16 and A20, together with the absence of cytotoxicity toward normal PBMCs at the nanomolar concentrations at which they modulated P-gp activity, highlights these artemisinin derivatives as promising scaffolds for the development of novel P-gp modulators. Collectively, the computational and experimental findings provide mechanistic insights into P-gp inhibition and establish a framework for the rational design of artemisinin-based P-gp modulators.",
  "abstract_shown": true,
  "affiliations": [
    "Universidad Católica de Córdoba Córdoba Argentina.",
    "Synthetic Organic Chemistry Laboratory, Department of Chemistry, University of Patras GR-26504 Patras Greece kath@upatras.gr.",
    "Institute of Chemistry and Biochemistry, IQUIBIM, College of Exact and Natural Sciences, Universidad Nacional de Mar del Plata - QUIAMM - INBIOTEC CONICET Mar del Plata Argentina dmavera@yahoo.com.",
    "Fine Chemical and Natural Products Laboratory, CIDIE CONICET-UCC, Universidad Católica de Córdoba Córdoba Argentina ceciliacarpinella@ucc.edu.ar."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jerónimo Laiolo",
      "orcid": "0000-0001-8971-9684"
    },
    {
      "affs": [
        1
      ],
      "name": "Artemis Tsirogianni"
    },
    {
      "affs": [
        2
      ],
      "name": "Cecilia L Barbieri"
    },
    {
      "affs": [
        3
      ],
      "name": "Mariana Belén Joray"
    },
    {
      "affs": [
        1
      ],
      "name": "Dafni G Graikioti",
      "orcid": "0000-0001-8057-0019"
    },
    {
      "affs": [
        1
      ],
      "name": "Dimitra Toumpa"
    },
    {
      "affs": [
        3
      ],
      "name": "Jazmín Lavallén"
    },
    {
      "affs": [
        2
      ],
      "name": "Nicolás A Rodriguez"
    },
    {
      "affs": [
        2
      ],
      "name": "D Mariano A Vera"
    },
    {
      "affs": [
        1
      ],
      "name": "Constantinos M Athanassopoulos",
      "orcid": "0000-0002-7549-1911"
    },
    {
      "affs": [
        3
      ],
      "name": "María C Carpinella",
      "orcid": "0000-0001-5553-1851"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2tth0de8sgtk6.bib",
  "cited_by": 0,
  "doi": "10.1039/d6ra07164c",
  "fulltext_url": "https://europepmc.org/articles/PMC13702068",
  "id": "2tth0de8sgtk6",
  "issns": [
    "2046-2069"
  ],
  "landing_url": "https://europepmc.org/article/MED/42936332",
  "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",
      "2730|Drug Transport and Resistance Mechanisms"
    ]
  ],
  "openalex": "W7223655854",
  "pdf_url": "https://europepmc.org/articles/PMC13702068?pdf=render",
  "pmcid": "PMC13702068",
  "pmid": "42936332",
  "published": "2026-10-26",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/2tth0de8sgtk6.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:12Z",
      "native_id": "MED:42936332",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42936332"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Drug Transport and Resistance Mechanisms",
      "subfield": "oncology"
    }
  ],
  "title": "Design, synthesis and biological evaluation of novel artemisinin derivatives as potent P-glycoprotein modulators for overcoming multidrug resistance.",
  "title_text": "Design, synthesis and biological evaluation of novel artemisinin derivatives as potent P-glycoprotein modulators for overcoming multidrug resistance.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:22:12Z",
  "url": "https://research.draconitic.com/paper/2tth0de8sgtk6",
  "venue": "RSC advances",
  "versions": []
}