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Divalent Naphthalene Diimide Ligands Display High Selectivity for the Human Telomeric G-quadruplex in K+ Buffer.

ABSTRACT: Selective G-quadruplex ligands offer great promise for the development of anti-cancer therapies. A novel series of divalent cationic naphthalene diimide ligands that selectively bind to the hybrid form of the human telomeric G-quadruplex in K+ buffer are described herein. We demonstrate that an imidazolium-bearing mannoside-conjugate is the most selective ligand to date for this quadruplex against several other quadruplex and duplex structures. We also show that a similarly selective methylpiperazine-bearing ligand was more toxic to HeLa cancer cells than doxorubicin, whilst exhibiting three times less toxicity towards fetal lung fibroblasts WI-38.

SUBMITTER: Street STG

PROVIDER: S-EPMC5485019 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Divalent Naphthalene Diimide Ligands Display High Selectivity for the Human Telomeric G-quadruplex in K<sup>+</sup> Buffer.

Street Steven T G STG Chin Donovan N DN Hollingworth Gregory J GJ Berry Monica M Morales Juan C JC Galan M Carmen MC

Chemistry (Weinheim an der Bergstrasse, Germany) 20170330 29

Selective G-quadruplex ligands offer great promise for the development of anti-cancer therapies. A novel series of divalent cationic naphthalene diimide ligands that selectively bind to the hybrid form of the human telomeric G-quadruplex in K<sup>+</sup> buffer are described herein. We demonstrate that an imidazolium-bearing mannoside-conjugate is the most selective ligand to date for this quadruplex against several other quadruplex and duplex structures. We also show that a similarly selective ...[more]

PMID: 28257554

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Mechanism of the antiproliferative activity of some naphthalene diimide G-quadruplex ligands.

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