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Molecules (Basel, Switzerland)
Nov 25, 2024;29 (23):

Exploring 4,7-Disubstituted Pyrimido[4,5-]pyrimidines as Antiviral and Anticancer Agents.

Eleftheria A Georgiou, Konstantinos Paraskevas, Christina Koutra, Leentje Persoons, Dominique Schols, Steven De Jonghe, Ioannis K Kostakis
Author Information
  1. Eleftheria A Georgiou: Department of Pharmacy, Division of Pharmaceutical Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, 15771 Athens, Greece. ORCID
  2. Konstantinos Paraskevas: Department of Pharmacy, Division of Pharmaceutical Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, 15771 Athens, Greece.
  3. Christina Koutra: Department of Pharmacy, Division of Pharmacognosy and Natural Products Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, 15771 Athens, Greece.
  4. Leentje Persoons: Molecular Genetics and Therapeutics in Virology and Oncology Research Group, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, Herestraat 49, P.O. Box 1043, 3000 Leuven, Belgium. ORCID
  5. Dominique Schols: Molecular Structural and Translational Virology Research Group, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, Herestraat 49, P.O. Box 1043, 3000 Leuven, Belgium. ORCID
  6. Steven De Jonghe: Molecular Structural and Translational Virology Research Group, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, Herestraat 49, P.O. Box 1043, 3000 Leuven, Belgium. ORCID
  7. Ioannis K Kostakis: Department of Pharmacy, Division of Pharmaceutical Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, 15771 Athens, Greece. ORCID
PMID: 39683709 DOI: 10.3390/molecules29235549

Abstract

Thirteen new 4,7-disubstituted pyrimido[4,5-]pyrimidines were synthesized via a straightforward methodology starting from thiourea. The anti-proliferative activity of these compounds was evaluated across a diverse panel of eight cancer cell lines, with derivatives and showing efficacy against several hematological cancer types. Furthermore, all compounds were assessed for their antiviral potency against a panel of viruses. Compounds featuring a cyclopropylamino group and an aminoindane moiety exhibited remarkable efficacy against human coronavirus 229E (HCoV-229E). These findings highlight the pyrimidino[4,5-]pyrimidine scaffold as an interesting framework for the design of novel antiviral agents against HCoVs, with compounds , , and emerging as strong candidates for further investigation.

Keywords

HCoV-229E anti-proliferative activity antiviral activity pyrimido[4,5-d]pyrimidines synthesis

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MeSH Term

Humans
Antiviral Agents
Antineoplastic Agents
Pyrimidines
Cell Line, Tumor
Structure-Activity Relationship
Cell Proliferation
Molecular Structure

Chemicals

Antiviral Agents
Antineoplastic Agents
Pyrimidines
Journal Article

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