Design, synthesis and evaluation of arylpurine-based sinefungin mimetics as zika virus methyltransferase inhibitors
Arylpurine derivatives were designed and synthesized to mimic sinefungin by targeting the SAM/SAH binding site of zika virus (ZIKV) methyltransferase (MTase). These compounds incorporate adenine or 6-methyl-7-deazapurine bases, while the ribose of sinefungin has been replaced by an aniline, linked to its amino acid chain <i>via</i> a CO or a CH<sub>2</sub> unit. Compounds 18, 29 and 31 inhibited ZIKV 2'-<i>O</i>-MTase activity. Docking studies showed that compounds 18 and 29 interact with both the purine and amino acid binding sites, effectively mimicking sinefungin. In contrast, compound 31 has its amino acid chain positioned above the ribose binding site. Notably, compound 18 exhibited modest antiviral activity against ZIKV.
Authors
- María‐Jesús Pérez‐Pérez (ORCID: https://orcid.org/0000-0003-1336-7760)
- Eva‐María Priego (ORCID: https://orcid.org/0000-0001-9470-4508)
- Suzanne J. F. Kaptein (ORCID: https://orcid.org/0000-0002-7935-0219)
- José-María Orduña (ORCID: https://orcid.org/0000-0003-4955-4998)
- Priscila Sutto‐Ortiz (ORCID: https://orcid.org/0000-0001-8672-690X)
- Étienne Decroly (ORCID: https://orcid.org/0000-0002-6046-024X)
- Natalia del Río (ORCID: https://orcid.org/0000-0002-6722-248X)
- Johan Neyts (ORCID: https://orcid.org/0000-0002-0033-7514)
- Iván Arribas‐Álvarez (ORCID: https://orcid.org/0009-0005-1723-4000)
Institutions
- Centre National de la Recherche Scientifique (FR)
- Aix-Marseille Université (FR)
- Rega Institute for Medical Research (BE)
- Instituto de Química Médica (ES)
- Architecture et Fonction des Macromolécules Biologiques (FR)
- Universidad Autónoma de Madrid (ES)
Publication Details
- Journal
- RSC Advances
- Published
- 2025-01-01
- DOI
- https://doi.org/10.1039/d5ra05362e
- Primary Topic
- Mosquito-borne diseases and control
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- European Commission
- Ministerio de Ciencia e Innovación
- HORIZON EUROPE Framework Programme
- European Regional Development Fund
- Agencia Estatal de Investigación