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

Salvatore Princiotto, Maria Karelou, Rachel Ioannidi, Giovanni Luca Beretta, Nadia Zaffaroni, Roberto Artali, Ioannis K Kostakis, Stefania Mazzini, Sabrina Dallavalle

Journal: International journal of molecular sciences 2023;24(18):14346

PMID: 37762650

Free Full Text on Archivio Istituzionale della Ricerca Unimi - Access Free Full Text View on PubMed

Abstract

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.

Address: Department of Food, Environmental and Nutritional Sciences (DeFENS), Università degli Studi di Milano, Via Celoria 2, 20133 Milan, Italy.; Department of Pharmacy, Division of Pharmaceutical Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, 15771 Athens, Greece.; Molecular Pharmacology Unit, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Via Amadeo 42, 20133 Milan, Italy.; Scientia Advice di Roberto Artali, 20832 Desio, Italy.

DOI: 10.3390/ijms241814346

Link outs

Free resources

Full Text Sources:

Medical:

https://medlineplus.gov/bonecancer.html

MeSH Terms: Humans, Cell Line, G-Quadruplexes, Osteosarcoma, Bone Neoplasms, Promoter Regions, Genetic