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

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.