Privileged Scaffold Decoration for the Identification of the First Trisubstituted Triazine with Anti-SARS-CoV-2 Activity

  • Molecules. 2022 Dec 12;27(24):8829. doi: 10.3390/molecules27248829.
Silvia Cesarini  1 ,  Ilaria Vicenti  2 ,  Federica Poggialini  3 ,  Massimiliano Secchi  4 ,  Federica Giammarino  2 ,  Ilenia Varasi  2 ,  Camilla Lodola  4 ,  Maurizio Zazzi  2 ,  Elena Dreassi  3 ,  Giovanni Maga  4 ,  Lorenzo Botta  1 ,  Raffaele Saladino  1
Affiliations
  • 1. Department of Biological and Ecological Sciences, University of Viterbo, Via S.C. De Lellis s.n.c., 01100 Viterbo, Italy.
  • 2. Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy.
  • 3. Department of Biotechnology, Chemistry, and Pharmacy (DBCF), University of Siena, 53100 Siena, Italy.
  • 4. Institute of Molecular Genetics, IGM CNR "Luigi Luca Cavalli-Sforza", Via Abbiategrasso 207, 27100 Pavia, Italy.
PMID: 36557962 DOI: 10.3390/molecules27248829
Abstract

Current therapy against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are based on the use of Remdesivir 1, Molnupiravir 2, and the recently identified Nirmatrelvir 3. Unfortunately, these three drugs showed some limitations regarding potency and possible drug-drug interactions. A series of derivatives coming from a decoration approach of the privileged scaffold s-triazines were synthesized and evaluated against SAR-CoV-2. One derivative emerged as the hit of the series for its micromolar Antiviral activity and low cytotoxicity. Mode of action and pharmacokinetic in vitro preliminary studies further confirm the role as candidates for a future optimization campaign of the most active derivative identified with this work.

Keywords
DDX3X; SARS-CoV-2; antivirals; decoration approach; privileged scaffold; s-triazines.
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