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萘二酰亚胺作为多模式 G-四链体选择性配体。

Naphthalene Diimides as Multimodal G-Quadruplex-Selective Ligands.

机构信息

Department of Chemistry, University of Pavia, Viale Taramelli 10, 27100 Pavia, Italy.

Department of Molecular Medicine, University of Padua, via A. Gabelli 63, 35121 Padua, Italy.

出版信息

Molecules. 2019 Jan 24;24(3):426. doi: 10.3390/molecules24030426.

Abstract

G-quadruplexes are four-stranded nucleic acids structures that can form in guanine-rich sequences. Following the observation that G-quadruplexes are particularly abundant in genomic regions related to cancer, such as telomeres and oncogenes promoters, several G-quadruplex-binding molecules have been developed for therapeutic purposes. Among them, naphthalene diimide derivatives have reported versatility, consistent selectivity and high affinity toward the G-quadruplex structures. In this review, we present the chemical features, synthesis and peculiar optoelectronic properties (absorption, emission, redox) that make naphtalene diimides so versatile for biomedical applications. We present the latest developments on naphthalene diimides as G-quadruplex ligands, focusing on their ability to bind G-quadruplexes at telomeres and oncogene promoters with consequent anticancer activity. Their different binding modes (reversible versus irreversible/covalent) towards G-quadruplexes and their additional use as antimicrobial agents are also presented and discussed.

摘要

四链体是由富含鸟嘌呤的序列形成的四条链的核酸结构。由于观察到四链体在与癌症相关的基因组区域(如端粒和致癌基因启动子)中特别丰富,因此已经开发了几种用于治疗目的的四链体结合分子。其中,萘二酰亚胺衍生物具有多功能性、一致的选择性和对四链体结构的高亲和力。在这篇综述中,我们介绍了使萘二酰亚胺在生物医学应用中如此多功能的化学特性、合成和独特的光电特性(吸收、发射、氧化还原)。我们介绍了作为四链体配体的萘二酰亚胺的最新进展,重点介绍了它们在端粒和致癌基因启动子上结合四链体的能力,从而具有抗癌活性。还介绍和讨论了它们对四链体的不同结合模式(可逆与不可逆/共价)及其作为抗菌剂的额外用途。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88d4/6384834/b7cffdec7ece/molecules-24-00426-g001.jpg

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