A hydrophilic three side-chained triazatruxene as a new strong and selective G-quadruplex ligand

Abstract

A new hydrosoluble triazatruxene derivative (Azatrux) is reported to selectively bind to G-quadruplex DNA, as derived by ESI-MS measurements and competition experiments.

Study of a Convenient Method for the Preparation of Hydrosoluble Fluorescent Triazatruxene Derivatives

“…As suggested by UV/Vis spectra registered at different temperatures [8] (also reproduced in the Supporting Information, Figure S1), these hydrophilic triazatruxene derivatives showed a poor tendency to aggregate in water solution, despite the large aromatic core. A confirmation of this behaviour was obtained by the observed linearity of absorbance versus concentration ( Figure 5), both in MES/KCl buffer (pH 6.5) and in a 0.1  aqueous solution of HCl.…”

“…[19] This could explain the good selectivity shown by AZATRUX for the G-quadruplex with respect to duplex DNA. [8] The synthesized triazatruxene derivatives also showed very interesting fluorescence properties. In fact, unsubstituted triazatruxene core 3 showed a very high fluorescence intensity in DMSO even at a low voltage (Figure 6a), as also reported for several other lipophilic N-substituted derivatives in organic solvents.…”

“…[7] We have recently reported a hydrophilic three side-chained triazatruxene as a new strong and selective G-quadruplex ligand, and thus potential anticancer drug. [8] Here, we consider different routes to obtain hydrosoluble triazatruxene derivatives in order to rationalize the different approaches present in the literature and define the most efficient method for the preparation of several compounds of this series and to analyze their spectroscopic properties.…”

Chemical Biology: What is Its Role in Drug Discovery?

“…The most strongly bound complex was shown to interact exclusively with the adenine nucleobases in the loop of the quadruplex. A novel potent and selective G-quadruplex ligand based on a trazatruxene core structure has been developed (Ginnari-Satriani et al, 2009). The ligand's anticancer activity has also been assessed.…”

Investigation of the interactions between methylene blue and intramolecular G-quadruplexes: an explicit distinction in electrochemical behavior

“…13 Until now, the interaction studies of MB and Gquadruplexes are mainly focused on a limited number of specific Gquadruplex-forming sequences and the studies of G-quadruplexes interaction with small molecules were usually carried out by nuclear magnetic resonance (NMR), mass spectroscopy (MS) and X-ray diffraction that require expensive equipment and considerable experimental time. [19][20][21] Here, we made use of the intrinsic electrochemical property of MB to systematically explore its binding mechanisms with a series of common intramolecular G-quadruplex sequences by electrochemical method, which has distinct advantages of simplicity, miniaturization, rapid response, low cost and that o l μL solutio as e ui ed fo the e pe i e ts p ese ted here. Compared with other works, 13,22,23 we used electrochemical method to distinguish the difference for binding affinities of MB with different intramolecular Gquadruplexes, which greatly enriched the study range of Gquadruplexes.…”