9,10-Bis[(4-(2-hydroxyethyl)piperazine-1-yl)prop-2-yne-1-yl]anthracene: Synthesis and G-quadruplex Selectivity

Giovanni Ribaudo,Maurizio Memo,Giuseppe Zagotto,Erika Oselladore,Alessandra Gianoncelli,Alberto Ongaro

doi:10.3390/m1138

Giovanni Ribaudo, Maurizio Memo + Show 4 more

Open Access

https://doi.org/10.3390/m1138

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Journal: Molbank	Publication Date: May 22, 2020
Citations: 1	License type: CC BY 4.0

Affiliation: University of Brescia, University of Padua

Abstract

G-quadruplex DNA is the target of several natural and synthetic small molecules with antiproliferative and antiviral activity. We here report the synthesis through Sonogashira reaction and A3 coupling of a disubstituted anthracene derivative, 9,10-bis[(4-(2-hydroxyethyl)piperazine-1-yl)prop-2-yne-1-yl]anthracene. The binding of this compound to G-quadruplex and double stranded DNA sequences was evaluated using electrospray ionization mass spectrometry (ESI-MS), demonstrating selectivity for the first structure. The interaction pattern of the ligand with G-quadruplex was investigated by molecular docking and stacking was found to be the preferred binding mode.

Highlights

G-quadruplex DNA represents an attractive target for small molecules in the context of drug discovery [1,2,3]
We previously presented a series of monosubstituted anthracene-propargylamine derivatives that were obtained through the A3 coupling reaction
Concerning DNA-binding properties, a set of electrospray ionization mass spectrometry (ESI-MS) experiments demonstrated a general preference for double stranded DNA (dsDNA) over G-quadruplex and an overall lack of selectivity [15]

Summary

Introduction

G-quadruplex DNA represents an attractive target for small molecules in the context of drug discovery [1,2,3]. These arrangements, constituted by stacked guanine nucleobases, can be formed by guanine-rich sequences, such as those that are present in telomeres, promoter genes and several viral genomes. Concerning DNA-binding properties, a set of electrospray ionization mass spectrometry (ESI-MS) experiments demonstrated a general preference for dsDNA over G-quadruplex and an overall lack of selectivity [15]. We here report the preparation of a novel disubstituted anthracene-propargylamine derivative through a multi-step approach and its preliminary evaluation as a G-quadruplex ligand by ESI-MS and molecular docking

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Results

Conclusion