{
  "abstract": "Malaria remains a major global health challenge worldwide and the emergence of resistance to frontline antimalarial drugs, including artemisinin-based combination therapies, underscores the need for novel antimalarial agents with distinct mechanism of action. Herein, eighteen novel 3H-1,5-benzodiazepine derivatives (5a-r) were synthesized and evaluated against chloroquine-sensitive (PfD10) and chloroquine resistant (PfW2) strains of Plasmodium falciparum. Cytotoxicity was assessed against human hepatocellular carcinoma (HepG2) cells to determine preliminary selectivity. Compound 5e, 5k, 5m, 5n, and 5o exhibited promising anti-plasmodial activity. Compound 5o was the most potent, with IC50 values of 5.88 ± 0.36 and 6.68 ± 2.03 µM against PfD10 and PfW2, respectively, whereas 5k and 5n displayed the most favourable selectivity profiles. Considering the potency of compounds 5k and 5o, we further evaluated them against human G9a, a histone lysine methyltransferase which showed exhibited weak inhibition relative to the reference inhibitor BIX-01294. Computational studies that include frontier molecular orbital analysis, molecular docking, MM-GBSA calculations, molecular dynamics simulations and post-simulation analyses were performed to support their binding modes and stability within the active sites of parasite-specific PfSET3 and human G9a. Thus, this study identifies 3H-1,5-benzodiazepine scaffold as a promising and underexplored starting point for new antimalarial agents, with PfSET3 emerging as an interesting target worth further investigation.",
  "abstract_shown": true,
  "affiliations": [
    "Medicinal Chemistry Research Laboratory",
    "Birla Institute of Technology and Science",
    "Department of Biomedical, Surgical and Dental Sciences, University of Milan, Pascal Street 36, Milan, Italy, 20133",
    "Cancer Pharmacology Division",
    "CSIR-Indian Institute of Integrative Medicine",
    "Academy of Scientific and Innovative Research (AcSIR",
    "Department of Chemistry",
    "Birla Institute of Technology and Science Pilani, Hyderabad Campus"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Pranali Vijaykumar Kuthe"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Mohammed Muzaffar-Ur-Rehman"
    },
    {
      "affs": [
        2
      ],
      "name": "Abirla Murugan"
    },
    {
      "affs": [
        3,
        4,
        5
      ],
      "name": "Mina Rashid"
    },
    {
      "affs": [
        2
      ],
      "name": "Nicoletta Basilico"
    },
    {
      "affs": [
        3,
        4,
        5
      ],
      "name": "Sajad Hussain Syed"
    },
    {
      "affs": [
        6,
        7
      ],
      "name": "Kondapalli Venkata Gowri Chandra Sekhar"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Sankaranarayanan Murugesan"
    },
    {
      "name": "Murugesan Sankaran",
      "orcid": "0000-0002-3680-1577"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dr4wh49bacbn6.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15010605/v1",
  "fulltext_url": null,
  "id": "dr4wh49bacbn6",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010605/v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2739|Malaria Research and Control"
    ]
  ],
  "openalex": "W7222565931",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15010605/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-16",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/dr4wh49bacbn6.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:24Z",
      "native_id": "10.26434/chemrxiv.15010605",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010605/v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2739|Malaria Research and Control",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "3H-1,5-Benzodiazepine Derivatives as Novel Antimalarial Agents: Synthesis, Biological Evaluation and Computational Target Exploration",
  "title_text": "3H-1,5-Benzodiazepine Derivatives as Novel Antimalarial Agents: Synthesis, Biological Evaluation and Computational Target Exploration",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:24Z",
  "url": "https://research.draconitic.com/paper/dr4wh49bacbn6",
  "venue": "ChemRxiv",
  "versions": []
}