1. Academic Validation
  2. In Silico Identification of Piperidinyl-amine Derivatives as Novel Dual Binders of Oncogene c-myc/c-Kit G-quadruplexes

In Silico Identification of Piperidinyl-amine Derivatives as Novel Dual Binders of Oncogene c-myc/c-Kit G-quadruplexes

  • ACS Med Chem Lett. 2018 Jul 10;9(8):848-853. doi: 10.1021/acsmedchemlett.8b00275.
Roberta Rocca 1 Federica Moraca 1 Giosuè Costa 1 Carmine Talarico 1 Francesco Ortuso 1 Silvia Da Ros 2 Giulia Nicoletto 2 Claudia Sissi 2 Stefano Alcaro 1 Anna Artese 1
Affiliations

Affiliations

  • 1 Dipartimento di Scienze della Salute, Università "Magna Graecia" di Catanzaro, Campus "Salvatore Venuta", Viale Europa, 88100 Catanzaro, Italy.
  • 2 Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, 35131 Padova, Italy.
Abstract

In the last years, it has been shown that the DNA secondary structure known as G-quadruplex is also involved in the regulation of oncogenes transcription, such as c-Myc, c-Kit, KRAS, Bcl-2, VEGF, and PDGF. DNA G-quadruplexes, formed in the promoter region of these proto-oncogenes, are considered alternative Anticancer targets since their stabilization causes a reduction of the related oncoprotein overexpression. In this study, a structure-based virtual screening toward the experimental DNA G-quadruplex structures of c-Myc and c-Kit was performed by using Glide for the docking analysis of a commercial library of approximately 693 000 compounds. The best hits were submitted to thermodynamic and biophysical studies, highlighting the effective stabilization of both G-quadruplex oncogene promoter structures for three N-(4-piperidinylmethyl)amine derivatives, thus proposed as a new class of dual G-quadruplex binders.

Figures