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Exploring the Interaction of New Pyridoquinazoline Derivatives with G-Quadruplex in the c-MYC Promoter Region.

Salvatore PrinciottoMaria KarelouRachel IoannidiGiovanni Luca BerettaNadia ZaffaroniRoberto ArtaliIoannis K KostakisStefania MazziniSabrina Dallavalle
Published in: International journal of molecular sciences (2023)
Novel amino-substituted pyridoquinazolinone derivatives have been designed and synthesized as potential c-MYC G-quadruplex (G4) ligands, employing an efficient methodology. All the new compounds exhibited moderate to good antiproliferative activity against the human osteosarcoma U2OS cell line. NMR and docking experiments revealed that the recently synthesized compounds interact with the Pu22 G-quadruplex in the c-MYC promoter region, establishing a 2:1 complex, with each molecule positioned over the tetrads at the 3'- and 5'-ends.
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