Publications by authors named "Jennifer S Butler"

9 Publications

  • Page 1 of 1

Platinum(IV)-azido monocarboxylato complexes are photocytotoxic under irradiation with visible light.

Dalton Trans 2021 Aug;50(30):10593-10607

Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, UK. and Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK.

Complexes trans,trans,trans-[Pt(N3)2(OH)(OCOR)(py)2] where py = pyridine and where OCOR = succinate (1); 4-oxo-4-propoxybutanoate (2) and N-methylisatoate (3) have been synthesized by derivation of trans,trans,trans-[Pt(OH)2(N3)2(py)2] (4) and characterised by NMR and EPR spectroscopy, ESI-MS and X-ray crystallography. Irradiation of 1-3 with green (517 nm) light initiated photoreduction to Pt(ii) and release of the axial ligands at a 3-fold faster rate than for 4. TD-DFT calculations showed dissociative transitions at longer wavelengths for 1 compared to 4. Complexes 1 and 2 showed greater photocytotoxicity than 4 when irradiated with 420 nm light (A2780 cell line IC50 values: 2.7 and 3.7 μM) and complex 2 was particularly active towards the cisplatin-resistant cell line A2780cis (IC50 3.7 μM). Unlike 4, complexes 1-3 were phototoxic under green light irradiation (517 nm), with minimal toxicity in the dark. A pKa(H2O) of 5.13 for the free carboxylate group was determined for 1, corresponding to an overall negative charge during biological experiments, which crucially, did not appear to impede cellular accumulation and photocytotoxicity.
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http://dx.doi.org/10.1039/d1dt01730fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8335519PMC
August 2021

Photoactivatable platinum anticancer complex can generate tryptophan radicals.

Chem Commun (Camb) 2018 Dec;54(98):13845-13848

Department of Physics, University of Warwick, CV4 7AL, Coventry, UK.

l-Tryptophan (Trp), melatonin (MLT) and the Trp-peptide pentagastrin quenched the formation of azidyl radicals generated on irradiation of the anticancer complex trans,trans,trans-[Pt(pyridine)2(N3)2(OH)2] with visible light, giving rise to C3-centred indole radicals which were characterized for Trp and MLT using an EPR spin-trap; indole, together with azidyl and hydroxyl radicals, have potential roles in a multitargeting mechanism of action against resistant cancers.
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http://dx.doi.org/10.1039/c8cc06496bDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6336088PMC
December 2018

The potent anti-cancer activity of Dioclea lasiocarpa lectin.

J Inorg Biochem 2017 10 16;175:179-189. Epub 2017 Jul 16.

Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK. Electronic address:

The lectin DLasiL was isolated from seeds of the Dioclea lasiocarpa collected from the northeast coast of Brazil and characterized for the first time by mass spectrometry, DNA sequencing, inductively coupled plasma-mass spectrometry, electron paramagnetic resonance, and fluorescence spectroscopy. The structure of DLasiL lectin obtained by homology modelling suggested strong conservation of the dinuclear Ca/Mn and sugar-binding sites, and dependence of the solvent accessibility of tryptophan-88 on the oligomerisation state of the protein. DLasiL showed highly potent (low nanomolar) antiproliferative activity against several human carcinoma cell lines including A2780 (ovarian), A549 (lung), MCF-7 (breast) and PC3 (prostate), and was as, or more, potent than the lectins ConBr (Canavalia brasiliensis), ConM (Canavalia maritima) and DSclerL (Dioclea sclerocarpa) against A2780 and PC3 cells. Interestingly, DLasiL lectin caused a G2/M arrest in A2780 cells after 24h exposure, activating caspase 9 and delaying the on-set of apoptosis. Confocal microscopy showed that fluorescently-labelled DLasiL localized around the nuclei of A2780 cells at lectin doses of 0.5-2× IC and gave rise to enlarged nuclei and spreading of the cells at high doses. These data reveal the interesting antiproliferative activity of DLasiL lectin, and suggest that further investigations to explore the potential of DLasiL as a new anticancer agent are warranted.
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http://dx.doi.org/10.1016/j.jinorgbio.2017.07.011DOI Listing
October 2017

[Fe(CN)5(isoniazid)](3-): an iron isoniazid complex with redox behavior implicated in tuberculosis therapy.

J Inorg Biochem 2014 Nov 12;140:236-44. Epub 2014 Aug 12.

Department of Chemistry, University of Warwick, Coventry CV4 7AL, United Kingdom. Electronic address:

Tuberculosis has re-emerged as a worldwide threat, which has motivated the development of new drugs. The antituberculosis complex Na3[Fe(CN)5(isoniazid)] (IQG607) in particular is of interest on account of its ability to overcome resistance. IQG607 has the potential for redox-mediated-activation, in which an acylpyridine (isonicotinoyl) radical could be generated without assistance from the mycobacterial KatG enzyme. Here, we have investigated the reactivity of IQG607 toward hydrogen peroxide and superoxide, well-known intracellular oxidizing agents that could play a key role in the redox-mediated-activation of this compound. HPLC, NMR and electronic spectroscopy studies showed a very fast oxidation rate for bound isoniazid, over 460-fold faster than free isoniazid oxidation. A series of EPR spin traps were used for detection of isonicotinoyl and derived radicals bound to iron. This is the first report for an isonicotinoyl radical bound to a metal complex, supported by (14)N and (1)H hyperfine splittings for the POBN and PBN trapped radicals. POBN and PBN exhibited average hyperfine coupling constants of aN=15.6, aH=2.8 and aN=15.4, aH=4.7, respectively, which are in close agreement to the isonicotinoyl radical. Radical generation is thought to play a major role in the mechanism of action of isoniazid and this work provides strong evidence for its production within IQG607, which, along with biological and chemical oxidation data, support a redox-mediated activation mechanism. More generally the concept of redox activation of metallo prodrugs could be applied more widely for the design of therapeutic agents with novel mechanisms of action.
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http://dx.doi.org/10.1016/j.jinorgbio.2014.08.002DOI Listing
November 2014

De novo generation of singlet oxygen and ammine ligands by photoactivation of a platinum anticancer complex.

Angew Chem Int Ed Engl 2013 Dec 25;52(51):13633-7. Epub 2013 Oct 25.

Department of Chemistry, University of Warwick, Coventry CV4 7AL (United Kingdom); Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190 (P.R. China).

Worth the excitement: Highly reactive oxygen and nitrogen species are generated by photoactivation of the anticancer platinum(IV) complex trans,trans,trans-[Pt(N3 )2 (OH)2 (MA)(Py)] (MA=methylamine, Py=pyridine). Singlet oxygen is formed from the hydroxido ligands and not from dissolved oxygen, and ammine ligands are products from the conversion of azido ligands to nitrenes. Both processes can induce oxidation of guanine.
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http://dx.doi.org/10.1002/anie.201307505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4230391PMC
December 2013

Reduction of quinones by NADH catalyzed by organoiridium complexes.

Angew Chem Int Ed Engl 2013 Apr 7;52(15):4194-7. Epub 2013 Mar 7.

Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK.

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http://dx.doi.org/10.1002/anie.201300747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3660790PMC
April 2013

Targeted delivery of platinum-based anticancer complexes.

Curr Opin Chem Biol 2013 Apr 7;17(2):175-88. Epub 2013 Feb 7.

Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK.

The most widely used anticancer drugs are platinum-based. Their efficacy might be improved by carriers which can transport large numbers of Pt centres, shield the drug from premature activation, and/or deliver Pt specifically to cancer cells using vectors which recognise specific targets. We describe recent progress using functionalized carbon nanotubes (CNTs) and nanorods, hollow Prussian blue (HPB), magnetic iron oxide and gold nanoparticles, liposomes, nanogels and polymers, as well as active targeting by conjugation to biodegradable proteins and peptides (e.g. EGF, heparin, herceptin, somatostatin and TAT). Spatially targeted activation of Pt(IV) prodrugs using light is also a promising approach. Interestingly, use of these new delivery and targeting systems for platinum drugs can lead to species with unusual reactivity which can kill cancer cells by new mechanisms.
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http://dx.doi.org/10.1016/j.cbpa.2013.01.004DOI Listing
April 2013

Tryptophan switch for a photoactivated platinum anticancer complex.

J Am Chem Soc 2012 Oct 25;134(40):16508-11. Epub 2012 Sep 25.

Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK.

The octahedral Pt(IV) complex trans,trans,trans-[Pt(N(3))(2)(OH)(2)(py)(2)] (1) is potently cytotoxic to cancer cells when irradiated with visible (blue) light. We show that the acute photocytotoxicity can be switched off by low doses (500 μM) of the amino acid l-tryptophan. EPR and NMR spectroscopic experiments using spin traps show that l-Trp quenches the formation of azidyl radicals, probably by acting as an electron donor. l-Trp is well-known as a mediator of electron transfer between distant electron acceptor/donor centers in proteins, and such properties may make the free amino acid clinically useful for controlling the activity of photochemotherapeutic azido Pt(IV) drugs. Since previous work has demonstrated the ability of photoactivated 1 to platinate DNA, this suggests that the high potency of such photoactive platinum complexes is related to their dual attack on cancer cells by radicals and Pt(II) photoproducts.
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http://dx.doi.org/10.1021/ja3074159DOI Listing
October 2012

Phosphorus leaching in manure-amended Atlantic Coastal Plain soils.

J Environ Qual 2005 Jan-Feb;34(1):370-81

Department of Natural Resource Sciences and Landscape Architecture, 0214 H.J. Patterson Hall, University of Maryland, College Park, MD 20742, USA.

Targeting the sources of phosphorus (P) and transport pathways of drainage from agricultural land will assist in the reduction of P loading to surface waters. Our research investigated the vertical movement of P from dairy manure and broiler litter through four Atlantic Coastal Plain soils. A randomized split-plot design with two main-plot tillage treatments (no tillage [NT] and chisel tillage [CH]) and five manure P rate split-plot treatments was used at each location. The split-plot P rates were 0, 100, 200, 300, and 400 kg P ha(-1) yr(-1). Four consecutive years of manure application began at all sites 5 yr before sampling. Soils were sampled to a depth of 150 cm from each split plot in seven depth increments and analyzed for soil test phosphorus (STP), water-extractable soil phosphorus (WSP), and degree of phosphorus saturation (DPS). The DPS of the 0- to 15-cm depths confirmed that at the 100 kg P ha(-1) yr(-1) application rate, all sites exceeded the threshold for P saturation (30%). At depths greater than 30 cm, DPS was typically below the 30% saturation threshold. The DPS change points ranged from 25 to 34% for the 0- to 90-cm depths. Our research concluded that the risk of P leaching through the matrix of the Atlantic Coastal Plain soils studied was not high; however, P leaching via macropore bypass may contribute to P loss from these soils.
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April 2005
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