Identification of Piperidinyl-amine Derivatives As Novel Dual Binders of Oncogene C-myc/c-Kit G-quadruplexes

Overview

Journal ACS Med Chem Lett

Publisher American Chemical Society

Specialty Chemistry

Date 2018 Aug 22

PMID 30128079

Citations 9

Authors

Roberta Rocca

Federica Moraca

Giosue Costa

Carmine Talarico

Francesco Ortuso

Silvia Da Ros

Giulia Nicoletto

Claudia Sissi

Stefano Alcaro

Anna Artese

Affiliations

Soon will be listed here.

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 , , , , , and . 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 and 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 -(4-piperidinylmethyl)amine derivatives, thus proposed as a new class of dual G-quadruplex binders.

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