Polypyridyl-Based Copper Phenanthrene Complexes: Combining Stability with Enhanced DNA Recognition.

Chemistry : a European Journal
Nicoló Zuin FantoniAndrew Kellett

Abstract

We report a series of copper(II) artificial metallo-nucleases (AMNs) and demonstrate their DNA damaging properties and in-vitro cytotoxicity against human-derived pancreatic cancer cells. The compounds combine a tris-chelating polypyridyl ligand, di-(2-pycolyl)amine (DPA), and a DNA intercalating phenanthrene unit. Their general formula is Cu-DPA-N,N' (where N,N'=1,10-phenanthroline (Phen), dipyridoquinoxaline (DPQ) or dipyridophenazine (DPPZ)). Characterisation was achieved by X-ray crystallography and continuous-wave EPR (cw-EPR), hyperfine sublevel correlation (HYSCORE) and Davies electron-nuclear double resonance (ENDOR) spectroscopies. The presence of the DPA ligand enhances solution stability and facilitates enhanced DNA recognition with apparent binding constants (Kapp ) rising from 105 to 107  m-1 with increasing extent of planar phenanthrene. Cu-DPA-DPPZ, the complex with greatest DNA binding and intercalation effects, recognises the minor groove of guanine-cytosine (G-C) rich sequences. Oxidative DNA damage also occurs in the minor groove and can be inhibited by superoxide and hydroxyl radical trapping agents. The complexes, particularly Cu-DPA-DPPZ, display promising anticancer activity against human pancreatic tumou...Continue Reading

References

Mar 1, 1991·In Vitro Cellular & Developmental Biology : Journal of the Tissue Culture Association·A Martin, M Clynes
Jul 4, 2002·Journal of the American Chemical Society·Kristi J HumphreysSteven E Rokita
Jul 15, 2004·Dalton Transactions : an International Journal of Inorganic Chemistry·Srecko I KirinNils Metzler-Nolte
Sep 28, 2005·Nucleic Acids Research·Brian C BalesMarc M Greenberg
Sep 29, 2005·Journal of Magnetic Resonance·Stefan Stoll, Arthur Schweiger
Jul 13, 2007·Nature Reviews. Cancer·Lloyd Kelland
Dec 25, 2007·Current Opinion in Chemical Biology·Pieter C A Bruijnincx, Peter J Sadler
Jan 27, 2010·Chemical Reviews·Marguerite Pitié, Geneviève Pratviel
May 13, 2011·The New England Journal of Medicine·Thierry ConroyUNKNOWN PRODIGE Intergroup
Apr 6, 2012·Journal of Applied Crystallography·Christian B HübschleBirger Dittrich
May 1, 2012·Chemical Communications : Chem Comm·Fabrizio MancinPaolo Tecilla
Feb 15, 2013·Chemical Communications : Chem Comm·Malachy McCannAndrew Kellett
May 3, 2013·Chemical Communications : Chem Comm·Nicolas P E Barry, Peter J Sadler
Oct 10, 2013·Chemical Reviews·Carlo SantiniCristina Marzano
May 9, 2014·Inorganic Chemistry·Zara MolphyAndrew Kellett
Dec 30, 2014·Acta Crystallographica. Section A, Foundations and Advances·George M Sheldrick
Jan 9, 2015·Acta Crystallographica. Section C, Structural Chemistry·George M Sheldrick
Jan 20, 2015·Dalton Transactions : an International Journal of Inorganic Chemistry·Jessica Nadine HamannFelix Tuczek
Jul 15, 2015·Chemical Communications : Chem Comm·Ruth LarragyAndrew Kellett
Jun 20, 2017·Dalton Transactions : an International Journal of Inorganic Chemistry·Zoi G LadaGeorge Mitrikas
Dec 10, 2017·Advances in Biological Regulation·Aleksandra AdamskaMarco Falasca
Apr 11, 2018·Dalton Transactions : an International Journal of Inorganic Chemistry·Rabbab OunNial J Wheate
Sep 18, 2018·Chemistry : a European Journal·Nicoló Zuin FantoniAndrew Kellett
Feb 5, 2019·Chemical Society Reviews·Andrew KellettNicholas P Farrell
Mar 6, 2019·World Journal of Oncology·Prashanth RawlaVinaya Gaduputi

❮ Previous
Next ❯

Citations

Feb 12, 2021·Chembiochem : a European Journal of Chemical Biology·Nicolò Zuin FantoniAndrew Kellett
Sep 28, 2021·Nucleic Acids Research·Natasha McStayAndrew Kellett

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

© 2022 Meta ULC. All rights reserved