Serendipitous Identification of Azine Anticancer Agents Using a Privileged Scaffold Morphing Strategy

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2024 Apr 13

PMID 38611732

Authors

Silvia Cesarini

Ilaria Vicenti

Federica Poggialini

Silvia Filippi

Eleonora Mancin

Lia Fiaschi

Elisa De Marchi

Federica Giammarino

Chiara Vagaggini

Bruno Mattia Bizzarri

Raffaele Saladino

Elena Dreassi

Maurizio Zazzi

Lorenzo Botta

Affiliations

Soon will be listed here.

Abstract

The use of privileged scaffolds as a starting point for the construction of libraries of bioactive compounds is a widely used strategy in drug discovery and development. Scaffold decoration, morphing and hopping are additional techniques that enable the modification of the chosen privileged framework and better explore the chemical space around it. In this study, two series of highly functionalized pyrimidine and pyridine derivatives were synthesized using a scaffold morphing approach consisting of triazine compounds obtained previously as antiviral agents. Newly synthesized azines were evaluated against lymphoma, hepatocarcinoma, and colon epithelial carcinoma cells, showing in five cases acceptable to good anticancer activity associated with low cytotoxicity on healthy fibroblasts. Finally, ADME in vitro studies were conducted on the best derivatives of the two series showing good passive permeability and resistance to metabolic degradation.

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