G‐Quadruplex DNA and its Ligands in Anticancer Therapy

Huang, Zhi‐Shu; Tan, Jia‐Heng; Ou, Tian‐Miao; Ding, Li; Gu, Lian‐Quan

doi:10.1002/9781118092804.ch5

Cited by 3 publications

(2 citation statements)

References 261 publications

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“…In 1997, Sun et al reported [38], for the first time, the inhibition of telomerase by interactive G-quadruplex ligands and, based on the results, anticipated the potential of the approach as a novel research line for anticancer drug design. Since then, the search for GQ interactive ligands with high specificity and affinity for GQ has become a central issue for different research groups [9,12,18,22,23,38,39].…”

Section: Interactive G-quadruplex Ligands and Gq Recognition Modesmentioning

confidence: 99%

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The Interactions of H2TMPyP, Analogues and Its Metal Complexes with DNA G-Quadruplexes—An Overview

et al. 2021

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The evidence that telomerase is overexpressed in almost 90% of human cancers justifies the proposal of this enzyme as a potential target for anticancer drug design. The inhibition of telomerase by quadruplex stabilizing ligands is being considered a useful approach in anticancer drug design proposals. Several aromatic ligands, including porphyrins, were exploited for telomerase inhibition by adduct formation with G-Quadruplex (GQ). 5,10,15,20-Tetrakis(N-methyl-4-pyridinium)porphyrin (H2TMPyP) is one of the most studied porphyrins in this field, and although reported as presenting high affinity to GQ, its poor selectivity for GQ over duplex structures is recognized. To increase the desired selectivity, porphyrin modifications either at the peripheral positions or at the inner core through the coordination with different metals have been handled. Herein, studies involving the interactions of TMPyP and analogs with different DNA sequences able to form GQ and duplex structures using different experimental conditions and approaches are reviewed. Some considerations concerning the structural diversity and recognition modes of G-Quadruplexes will be presented first to facilitate the comprehension of the studies reviewed. Additionally, considering the diversity of experimental conditions reported, we decided to complement this review with a screening where the behavior of H2TMPyP and of some of the reviewed metal complexes were evaluated under the same experimental conditions and using the same DNA sequences. In this comparison under unified conditions, we also evaluated, for the first time, the behavior of the AgII complex of H2TMPyP. In general, all derivatives showed good affinity for GQ DNA structures with binding constants in the range of 106–107 M−1 and ligand-GQ stoichiometric ratios of 3:1 and 4:1. A promising pattern of selectivity was also identified for the new AgII derivative.

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Section: Interactive G-quadruplex Ligands and Gq Recognition Modesmentioning

confidence: 99%

“…Figure 5. Anti and syn conformation of glycosidic torsion angles and groove sizes of parallel and anti-parallel GQ structures, (figure reused from[18], with permission from John Wiley and Sons.…”

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The Interactions of H2TMPyP, Analogues and Its Metal Complexes with DNA G-Quadruplexes—An Overview

et al. 2021

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Ligand Binding to Nucleic Acids

Brodbelt

2014

Physical Chemistry in Action

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Macrocyclic biphenyl tetraoxazoles: Synthesis, evaluation as G-quadruplex stabilizers and cytotoxic activity

Blankson

Pilch²,

Liu³

et al. 2013

Bioorganic & Medicinal Chemistry

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A series of macrocyclic biphenyl tetraoxazoles was synthesized. The latter stages of the synthetic approach allowed for the addition of varied N-protected α-amino acids, which were subsequently deprotected and condensed to provide the desired macrocycles. Improved yields could be realized in the macrocyclization step of their synthesis relative to other macrocyclic G-quadruplex stabilizers. These 24-membered macrocycles were evaluated for their ability to stabilize G-quadruplex DNA and for their relative cytotoxicity against human tumor cells. These biphenyl tetraoxazoles were not strong ligands for G-quadruplex DNA relative to other macrocyclic polyoxazoles. This reduced stabilizing potential did correlate with their comparatively lower cytotoxic activity as observed in the human tumor cell lines, RPMI 8402 and KB3-1. These studies provide useful insights into the conformational requirements for the development of selective and more potent G-quadruplex ligands.

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G‐Quadruplex DNA and its Ligands in Anticancer Therapy

Cited by 3 publications

References 261 publications

The Interactions of H2TMPyP, Analogues and Its Metal Complexes with DNA G-Quadruplexes—An Overview

The Interactions of H2TMPyP, Analogues and Its Metal Complexes with DNA G-Quadruplexes—An Overview

Ligand Binding to Nucleic Acids

Macrocyclic biphenyl tetraoxazoles: Synthesis, evaluation as G-quadruplex stabilizers and cytotoxic activity

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