CNR ExploRA

Articolo in rivista, 2022, ENG, 10.3390/molecules27248829

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

Cesarini S, Vicenti I, Poggialini F, Secchi M, Giammarino F, Varasi I, Lodola C, Zazzi M, Dreassi E, Maga G, Botta L, Saladino R

Department of Biological and Ecological Sciences, University of Viterbo, Via S.C. De Lellis s.n.c, Viterbo, 01100, Department of Biological and Ecological Sciences, University of Viterbo, Via S.C. De Lellis s.n.c, Viterbo, 01100, Italy, , Italy; Department of Medical Biotechnologies, University of Siena, Siena, 53100, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy, , Italy; Department of Biotechnology, Chemistry, and Pharmacy (DBCF), University of Siena, Siena, 53100, Department of Biotechnology, Chemistry, and Pharmacy (DBCF), University of Siena, Siena, 53100, Italy, , Italy; Institute of Molecular Genetics, IGM CNR "Luigi Luca Cavalli-Sforza", Via Abbiategrasso 207, Pavia, 27100, Institute of Molecular Genetics, IGM CNR "Luigi Luca Cavalli-Sforza", Via Abbiategrasso 207, Pavia, 27100, Italy, , Italy

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.

Molecules (Basel, Online) 27 (24)