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Special Issue "G-Quadruplex Ligands and Cancer"

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (30 December 2017)

Special Issue Editor

Guest Editor
Prof. Danzhou Yang

Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, Purdue Center for Cancer Research, 201 S. University St., West Lafayette, IN 47907, USA
Website | E-Mail
Interests: DNA structures and functions; G-quadruplexes; anticancer drugs; NMR; ligand interactions

Special Issue Information

Dear Colleagues,

G-quadruplexes are four-stranded nucleic acid secondary structures, which form in guanine-rich DNA and RNA sequences. Once a laboratory curiosity, these non-canonical structures are now known to form readily under physiological conditions in regions of biological significance, such as human telomeres, oncogene promoter regions, replication initiation sites, and 5’ and 3’-untranslated (UTR) regions. Many G-quadruplex forming sequences are found to be associated with cancer, thus, these non-canonical nucleic acid structures are considered to be attractive molecular targets for cancer therapeutics with novel mechanisms of action. In recent years, G-quadruplexes have received elevated research interest, and G-quadruplex interactive ligands have been identified to exhibit antiproliferative and chemosensitizing effects against tumor models both in vitro and in vivo. Notably, quarfloxin, a G-quadruplex-interactive fluoroquinoline derivative, reached phase II clinical trials for the treatment of carcinoid/neuroendocrine tumors. While significant advances have been made towards targeting G-quadruplex structures, many questions and challenges on the subject remain to be addressed. This Special Issue aims to provide opportunity to share new findings and recent advances on G-quadruplex targeted small-molecules toward the development of new anticancer drugs.

Prof. Danzhou Yang
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • G-quadruplexes nucleic acid secondary structures
  • molecular targets for cancer therapeutics
  • G-quadruplex-targeted ligands
  • anticancer and chemosensitizing effects

Published Papers (2 papers)

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Research

Open AccessArticle Design, Synthesis and Biological Evaluation of New Substituted Diquinolinyl-Pyridine Ligands as Anticancer Agents by Targeting G-Quadruplex
Molecules 2018, 23(1), 81; doi:10.3390/molecules23010081
Received: 8 December 2017 / Revised: 20 December 2017 / Accepted: 29 December 2017 / Published: 30 December 2017
PDF Full-text (2846 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
G-quadruplexes (G4) are stacked non-canonical nucleic acid structures found in specific G-rich DNA or RNA sequences in the human genome. G4 structures are liable for various biological functions; transcription, translation, cell aging as well as diseases such as cancer. These structures are therefore
[...] Read more.
G-quadruplexes (G4) are stacked non-canonical nucleic acid structures found in specific G-rich DNA or RNA sequences in the human genome. G4 structures are liable for various biological functions; transcription, translation, cell aging as well as diseases such as cancer. These structures are therefore considered as important targets for the development of anticancer agents. Small organic heterocyclic molecules are well known to target and stabilize G4 structures. In this article, we have designed and synthesized 2,6-di-(4-carbamoyl-2-quinolyl)pyridine derivatives and their ability to stabilize G4-structures have been determined through the FRET melting assay. It has been established that these ligands are selective for G4 over duplexes and show a preference for the parallel conformation. Next, telomerase inhibition ability has been assessed using three cell lines (K562, MyLa and MV-4-11) and telomerase activity is no longer detected at 0.1 μM concentration for the most potent ligand 1c. The most promising G4 ligands were also tested for antiproliferative activity against the two human myeloid leukaemia cell lines, HL60 and K562. Full article
(This article belongs to the Special Issue G-Quadruplex Ligands and Cancer)
Figures

Figure 1

Open AccessArticle Investigation of ‘Head-to-Tail’-Connected Oligoaryl N,O-Ligands as Recognition Motifs for Cancer-Relevant G-Quadruplexes
Molecules 2017, 22(12), 2160; doi:10.3390/molecules22122160
Received: 27 October 2017 / Revised: 22 November 2017 / Accepted: 2 December 2017 / Published: 6 December 2017
PDF Full-text (2287 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Oligomeric compounds, constituted of consecutive N,O-heteroaromatic rings, introduce useful and tunable properties as alternative ligands for biomolecular recognition. In this study, we have explored a synthetic scheme relying on Van Leusen oxazole formation, in conjunction with C–H activation of the
[...] Read more.
Oligomeric compounds, constituted of consecutive N,O-heteroaromatic rings, introduce useful and tunable properties as alternative ligands for biomolecular recognition. In this study, we have explored a synthetic scheme relying on Van Leusen oxazole formation, in conjunction with C–H activation of the formed oxazoles and their subsequent C–C cross-coupling to 2-bromopyridines in order to assemble a library of variable-length, ‘head-to-tail’-connected, pyridyl-oxazole ligands. Through investigation of the interaction of the three longer ligands (5-mer, 6-mer, 7-mer) with cancer-relevant G-quadruplex structures (human telomeric/22AG and c-Myc oncogene promoter/Myc2345-Pu22), the asymmetric pyridyl-oxazole motif has been demonstrated to be a prominent recognition element for G-quadruplexes. Fluorescence titrations reveal excellent binding affinities of the 7-mer and 6-mer for a Na+-induced antiparallel 22AG G-quadruplex (KD = 0.6 × 10−7 M−1 and 0.8 × 10−7 M−1, respectively), and satisfactory (albeit lower) affinities for the 22AG/K+ and Myc2345-Pu22/K+ G-quadruplexes. All ligands tested exhibit substantial selectivity for G-quadruplex versus duplex (ds26) DNA, as evidenced by competitive Förster resonance energy transfer (FRET) melting assays. Additionally, the 7-mer and 6-mer are capable of promoting a sharp morphology transition of 22AG/K+ G-quadruplex. Full article
(This article belongs to the Special Issue G-Quadruplex Ligands and Cancer)
Figures

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