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Full-Text Articles in Medicinal-Pharmaceutical Chemistry

Poly(Ethylene Glycol)-Based Peptidomimetic "Pegtide" Of Oligo-Arginine Allows For Efficient Sirna Transfection And Gene Inhibition., Alan Hibbitts, Aoife M O'Connor, Joanna Mccarthy, Éanna B Forde, Gary Hessman, Caitriona M O'Driscoll, Sally-Ann Cryan, Marc Devocelle Jun 2019

Poly(Ethylene Glycol)-Based Peptidomimetic "Pegtide" Of Oligo-Arginine Allows For Efficient Sirna Transfection And Gene Inhibition., Alan Hibbitts, Aoife M O'Connor, Joanna Mccarthy, Éanna B Forde, Gary Hessman, Caitriona M O'Driscoll, Sally-Ann Cryan, Marc Devocelle

Chemistry Articles

While a wide range of experimental and commercial transfection reagents are currently available, persistent problems remain regarding their suitability for continued development. These include the transfection efficiency for difficult-to-transfect cell types and the risks of decreased cell viability that may arise from any transfection that does occur. Therefore, research is now turning toward alternative molecules that improve the toxicity profile of the gene delivery vector (GDV), while maintaining the transfection efficiency. Among them, cell-penetrating peptides, such as octa-arginine, have shown significant potential as GDVs. Their pharmacokinetic and pharmacodynamic properties can be enhanced through peptidomimetic conversion, whereby a peptide is modified ...


Nonlinear Optical Measurements Of Bf2–Aza Dipyrromethene Fluorophores., Fryad Z. Henari, Donal F. O'Shea, Dan Wu Apr 2019

Nonlinear Optical Measurements Of Bf2–Aza Dipyrromethene Fluorophores., Fryad Z. Henari, Donal F. O'Shea, Dan Wu

Chemistry Articles

Nonlinear absorption coefficient and the nonlinear refractive index of a series of BF2 aza dipyrromethene chromophores in tetrahydrofuran (THF) solutions were measured using the Z-scan technique with a low power continuous wave laser at 633 nm. Acquired data illustrated that the process involved in nonlinear absorption is reverse saturation absorption. The excited state absorption cross sections for all complexes were calculated and a pump and probe technique was used to record the triplet absorption spectrum. The band gap of the triplet state was estimated from this spectral data and the optical limiting behavior was demonstrated for each derivative.


Qualitative And Quantitative Ethnobotanical Study Of The Pangkhua Community In Bilaichari Upazilla, Rangamati District, Bangladesh., Mohammad O. Faruque, Gang Feng, Md Na Khan, James W. Barlow, Umme R. Ankhi, Sheng Hu, M Kamaruzzaman, Shaikh B. Uddin, Xuebo Hu Feb 2019

Qualitative And Quantitative Ethnobotanical Study Of The Pangkhua Community In Bilaichari Upazilla, Rangamati District, Bangladesh., Mohammad O. Faruque, Gang Feng, Md Na Khan, James W. Barlow, Umme R. Ankhi, Sheng Hu, M Kamaruzzaman, Shaikh B. Uddin, Xuebo Hu

Chemistry Articles

BACKGROUND: The present study documents the ethnomedicinal knowledge among the traditional healers of the Pangkhua indigenous community of Bangladesh. The documented data from this area was quantitatively analyzed for the first time. We aimed to record ethnomedicinal information from both the traditional healers and also the elderly men and women of the community, in order to compile and document all available information concerning plant use and preserve it for the coming generations. We aimed to compare how already known species are used compared to elsewhere and particularly to highlight new ethnomedicinal plant species alongside their therapeutic use(s).

METHODS: All ...


Rgd Conjugated Cell Uptake Off To On Responsive Nir-Aza Fluorophores: Applications Toward Intraoperative Fluorescence Guided Surgery, Dan Wu, Harrison C. Daly, Marco Grossi, Emer Conroy, Bo Li, William M. Gallagher, Robert Elmes, Donal F. O'Shea Jan 2019

Rgd Conjugated Cell Uptake Off To On Responsive Nir-Aza Fluorophores: Applications Toward Intraoperative Fluorescence Guided Surgery, Dan Wu, Harrison C. Daly, Marco Grossi, Emer Conroy, Bo Li, William M. Gallagher, Robert Elmes, Donal F. O'Shea

Chemistry Articles

The use of NIR-fluorescence imaging to demarcate tumour boundaries for real-time guidance of their surgical resection has a huge untapped potential. However, fluorescence imaging using molecular fluorophores, even with a targeting biomolecule attached, has a major shortcoming of signal interference from non-specific background fluorescence outside the region of interest. This poor selectivity necessitates prolonged time delays to allow clearance of background fluorophore and retention within the tumour prior to image acquisition. In this report, an innovative approach to overcome this issue is described in which cancer targeted off to on bio-responsive NIRfluorophores are utilised to switch-on first within the tumour ...


Au(Iii) And Pt(Ii) Complexes Of A Novel And Versatile 1,4-Disubstituted 1,2,3-Triazole-Based Ligand Possessing Diverse Secondary And Tertiary Coordinating Groups., Eolann Kitteringham, Zehao Zhou, Brendan Twamley, Darren M. Griffith Oct 2018

Au(Iii) And Pt(Ii) Complexes Of A Novel And Versatile 1,4-Disubstituted 1,2,3-Triazole-Based Ligand Possessing Diverse Secondary And Tertiary Coordinating Groups., Eolann Kitteringham, Zehao Zhou, Brendan Twamley, Darren M. Griffith

Chemistry Articles

A novel 1,4-disubstituted 1,2,3-triazole-based ligand, 2-(4-(pyridin-2-yl)-1 H-1,2,3-triazol-1-yl)propane-1,3-diamine (ptpd), which possesses pyridyl and diamino secondary and tertiary coordinating groups was synthesized in excellent yield. The reactivity of 2-(1-phenyl-1 H-1,2,3-triazol-4-yl)pyridine (ptp), di- tert-butyl (2-azidopropane-1,3-diyl)dicarbamate (Boc


Real-Time Recording Of The Cellular Effects Of The Anion Transporter Prodigiosin., Shane Cheung, Dan Wu, Harrison C. Daly, Nathalie Busschaert, Marina Morgunova, Jeremy C. Simpson, Dimitri Scholz, Philip A. Gale, Donal F. O'Shea Apr 2018

Real-Time Recording Of The Cellular Effects Of The Anion Transporter Prodigiosin., Shane Cheung, Dan Wu, Harrison C. Daly, Nathalie Busschaert, Marina Morgunova, Jeremy C. Simpson, Dimitri Scholz, Philip A. Gale, Donal F. O'Shea

Chemistry Articles

The unraveling of the cellular effects of anion transporters is key to their potential development as apoptosis-inducing or autophagy-disrupting therapeutics. Here, we conducted a systematic study of the cellular responses to the anion transporter prodigiosin by using a pH on/off responsive near-infrared (NIR)-fluorescent probe in HeLa and LAMP1-GFP-transfected HeLa cell lines. The sequence of localized and global cellular acidity changes and the resulting outcomes induced by the anion transporter were visualized with high temporal and spatial resolution. The results show that prodigiosin causes the pH within the lysosomal lumen to rise, after which a non-organelle-specific increase in acidity ...


Development Of A Novel Carboplatin Like Cytoplasmic Trackable Near Infrared Fluorophore Conjugate Via Strain-Promoted Azide Alkyne Cycloaddition., Eolann Kitteringham, Dan Wu, Shane Cheung, Brendan Twamley, Donal F. O'Shea, Darren M. Griffith Feb 2018

Development Of A Novel Carboplatin Like Cytoplasmic Trackable Near Infrared Fluorophore Conjugate Via Strain-Promoted Azide Alkyne Cycloaddition., Eolann Kitteringham, Dan Wu, Shane Cheung, Brendan Twamley, Donal F. O'Shea, Darren M. Griffith

Chemistry Articles

The successful design and pre-clicked synthesis of a non-toxic and cytosol trackable carboplatin-like near infrared fluorophore conjugate via strain-promoted azide alkyne cycloaddition (SPAAC) is reported. Reaction of cis-[Pt(2-azidopropane-1,3-diamine)(cbdca)] (cbdca = cyclobutane-1,1-dicarboxylato) and a bicyclo[6.1.0]non-4-yne near-infrared (NIR) azadipyrromethene fluorophore gave the corresponding clicked Pt-Fluorophore conjugate. The X-ray crystal structure of cis-[Pt(2-azidopropane-1,3-diamine)(cbdca)] was determined featuring the azide on the bidentate 1,3-diaminopropane ligand. The Pt-fluorophore conjugate is the first example of a Pt conjugate clicked via strain-promoted azide alkyne cycloaddition (SPAAC) where the reactive azide handle is on the amine ...


Directed Self-Assembly Of Fluorescence Responsive Nanoparticles And Their Use For Real-Time Surface And Cellular Imaging., Shane Cheung, Donal F. O'Shea Dec 2017

Directed Self-Assembly Of Fluorescence Responsive Nanoparticles And Their Use For Real-Time Surface And Cellular Imaging., Shane Cheung, Donal F. O'Shea

Chemistry Articles

Directed self-assemblies in water are known as the most efficient means of forming complex higher ordered structures in nature. Here we show a straightforward and robust method for particle assembly which utilises the amphiphilic tri-block co-polymer poloxamer-188 and a hydrophobic fluorophore as the two designer components, which have a built-in ability to convey spatial and temporal information about their surroundings to an observer. Templating of particle self-assembly is attributed to interactions between the fluorophore and hydrophobic segment of the poloxamer. Particle fluorescence in water is quenched but can be induced to selectively switch on in response to temperature, surface adsorption ...


Platinum(Iv) Oxaliplatin-Peptide Conjugates Targeting Memhsp70+ Phenotype In Colorectal Cancer Cells., Aoife M. Mckeon, Janis Noonan, Marc Devocelle, Brona M. Murphy, Darren M. Griffith Oct 2017

Platinum(Iv) Oxaliplatin-Peptide Conjugates Targeting Memhsp70+ Phenotype In Colorectal Cancer Cells., Aoife M. Mckeon, Janis Noonan, Marc Devocelle, Brona M. Murphy, Darren M. Griffith

Chemistry Articles

Novel Pt(iv) tumour penetrating peptide (TPP) conjugates are reported. They are the first example of metallodrugs to target a membrane bound heat shock protein 70 positive (memHSP70+) phenotype in cancer cells. The conjugates exhibit superior cytotoxicity as compared to oxaliplatin alone in Pt resistant colorectal cancer cells with relatively high memHSP70+ expression. Substitution of TPP in Pt(iv) peptide conjugates with scrambled peptide (ScP) essentially abolishes the observed cytotoxicity.


Bf2-Azadipyrromethene Nir-Emissive Fluorophores With Research And Clinical Potential., Harrison C. Daly, Gonzalo Sampedro, Corentin Bon, Dan Wu, Ghazi Ismail, Ronan A. Cahill, Donal F. O'Shea Jul 2017

Bf2-Azadipyrromethene Nir-Emissive Fluorophores With Research And Clinical Potential., Harrison C. Daly, Gonzalo Sampedro, Corentin Bon, Dan Wu, Ghazi Ismail, Ronan A. Cahill, Donal F. O'Shea

Chemistry Articles

The use of near-infrared fluorescence for in vivo research and intraoperative clinical imaging is rapidly expanding, with new applications being proposed and developed. While imaging hardware and software have significantly progressed in recent times, the molecular fluorescent agents remain a limiting factor. In this report, the design, synthesis, photophysical characterization and bio-medical imaging assessment of two new NIR-fluorophores based on the BF


Fluorogenic Nir-Probes Based On 1,2,4,5-Tetrazine Substituted Bf2-Azadipyrromethenes, Dan Wu, Donal F. O'Shea Jan 2017

Fluorogenic Nir-Probes Based On 1,2,4,5-Tetrazine Substituted Bf2-Azadipyrromethenes, Dan Wu, Donal F. O'Shea

Chemistry Articles

A series of 1,2,4,5-tetrazine integrated near infrared (NIR) fluorophores based on the BF2 azadipyrromethene (NIR-AZA) class has been synthesised and their ability to modulate emission from low to high in response to Diels-Alder cycloaditions has been assessed. Substituents on the tetrazine component of the probe (Cl, OMe, p-NO2C6H4O) were seen to strongly influence quantum yields, fluorescence enhancement factors, and rates of cycloadditions. Cycloadditions between tetrazine-NIR-AZA constructs and a strained alkyne substrate were seen to be highly efficient in organic or aqueous solutions and in gels with high fluorescence enhancements of up to 48-fold observed. Real-time demonstration of ...


Polymer Brush Decorated Nanoparticles Immobilised On Polymer Monoliths For Enhanced Biopolymer Elution, M Iacono, D Connolly, Andreas Heise Jan 2017

Polymer Brush Decorated Nanoparticles Immobilised On Polymer Monoliths For Enhanced Biopolymer Elution, M Iacono, D Connolly, Andreas Heise

Chemistry Articles

A protocol for the decoration of a polymeric monolith with polymer brush grafted silica nanoparticles was developed. Monolithic poly(glycidyl methacrylate-co-ethylene glycol dimethacrylate) (GMA-co-EDMA) was prepared in 15 mm long cylindrical polypropylene tubing and quarternized. 160 nm silica nanoparticles with a 20 nm poly(methacrylic acid-co-tert-butyl methacrylate) brush layer were flushed through the monolith and electrostatically trapped. A uniform and dense carboxylic acid containing brush nanoparticle surface decoration over the entire length of the monolith was achieved. Elution performance of the brush nanoparticle decorated monolith was compared to a carboxylic acid surface decorated monolith ...


Mandelic Acid Derived Ionic Liquids: Synthesis, Toxicity And Biodegradability, Hannah Prydderch, Annette Haib, Marcel Spulak, Brid Quilty, Klaus Kummerer, Andreas Heise, Nicholas Gathergood Jan 2017

Mandelic Acid Derived Ionic Liquids: Synthesis, Toxicity And Biodegradability, Hannah Prydderch, Annette Haib, Marcel Spulak, Brid Quilty, Klaus Kummerer, Andreas Heise, Nicholas Gathergood

Chemistry Articles

A series of ten ionic liquids (ILs) was synthesised from the renewable resource mandelic acid. The ILs showed low antimicrobial activity towards the thirteen bacterial and twelve fungal strains they were screened against. A general trend of increasing bacterial toxicity in the order methyl ester < ethyl ester < n-butyl ester/amide was observed. IL biodegradability was evaluated using the Closed Bottle test (OECD 301D). Biodegradation increased in the order of increasing alkyl chain length for the ester ILs (methyl < ethyl < n-butyl). Despite none of the ILs presenting as readily biodegradable (>60% in 28 days), a series of biodegradation transformation products has been proposed based on the degradation of the ester/ amide alkyl chain. This data has allowed for an assessment of the effect of IL structural features on toxicity and biodegradation, particularly allowing for a comparison to earlier work where additional oxygen atoms were present ...


Polymeric Prodrug Combination To Exploit The Therapeutic Potential Of Antimicrobial Peptides Against Cancer Cells., Graeme J. Kelly, A Foltyn-Arfa Kia, F Hassan, S O'Grady, Maria P. Morgan, B S. Creaven, S Mcclean, Judith H. Harmey, Marc Devocelle Oct 2016

Polymeric Prodrug Combination To Exploit The Therapeutic Potential Of Antimicrobial Peptides Against Cancer Cells., Graeme J. Kelly, A Foltyn-Arfa Kia, F Hassan, S O'Grady, Maria P. Morgan, B S. Creaven, S Mcclean, Judith H. Harmey, Marc Devocelle

Chemistry Articles

Antimicrobial Peptides (AMPs) have unique anticancer properties, but their clinical application is currently limited by an inadequate margin of safety. A prodrug strategy associated with a combination therapy approach could address this limitation by increasing their therapeutic index and their efficacy. Accordingly, the first targeted anticancer polymeric prodrug candidates of AMPs, intended for combination therapy with another polymeric prodrug of an approved antineoplastic agent (doxorubicin), were synthesized as either a PEG-based dual-release prodrug or two individual pegylated prodrugs. The latter are based on a cathepsin B-labile peptide linker and an acid-sensitive acyl hydrazone bond for the AMP and doxorubicin prodrugs ...


Strained Alkyne Substituted Near Infrared Bf2 Azadipyrromethene Fluorochrome, Dan Wu, Shane Cheung, Corry James O'Sullivan, Yinghua Gao, Zhi-Long Chen, Donal F. O'Shea Sep 2016

Strained Alkyne Substituted Near Infrared Bf2 Azadipyrromethene Fluorochrome, Dan Wu, Shane Cheung, Corry James O'Sullivan, Yinghua Gao, Zhi-Long Chen, Donal F. O'Shea

Chemistry Articles

The contribution of imaging with near infrared (NIR) fluorophores to the elucidation of complex biological processes continues to rapidly expand. New tools for mild selective bioconjugation are strongly desirable for the construction of NIR labelled biomolecules. This work presents the synthesis and evaluation of a strained alkyne substituted NIR BF2-azadipyrromethene (NIR-AZA) which can conjugate in water with azido-homoalanine and cRGD peptide within 30 min at rt. Imaging analysis of the NIR-AZA–cRGD conjugate in vitro and in vivo showed efficient cellular uptake and good in vivo tumor targeting properties, illustrating the potential for translation to clinical imaging.


Synthesis Of Polymeric Bismuth Chlorido Hydroxamato Complexes; X-Ray Crystal Structure And Antibacterial Activity Of A Novel Bi(Lll) Salicylhydroxamato Complex, Donal M. Keoghan, Lauren E. Fagan, Thayse Marques Passos, Helge Müller-Bunz, Bríd Quilty, Darren M. Griffith Sep 2016

Synthesis Of Polymeric Bismuth Chlorido Hydroxamato Complexes; X-Ray Crystal Structure And Antibacterial Activity Of A Novel Bi(Lll) Salicylhydroxamato Complex, Donal M. Keoghan, Lauren E. Fagan, Thayse Marques Passos, Helge Müller-Bunz, Bríd Quilty, Darren M. Griffith

Chemistry Articles

Reaction of salicylhydroxamic acid (Sha) and 2-aminophenyl hydroxamic acid (2-NH2-pha) with BiCl3 affords the corresponding novel polymeric bismuth chlorido hydroxamato complexes; [BiCl2(-Sha-1H)]∞ and [BiCl3(--Pha-1H)]∞ respectively. The X-ray crystal structure of the THF-solvated polymeric bismuth chlorido salicylhydroxamato complex, [BiCl2(-Sha-1H)(THF)]∞ was solved, confirming the polymeric structure of this class of compounds and the (O,μ-O’)-bidentate bridging coordination mode of the hydroxamato ligand. The antibacterial activity of the THF-free polymeric bismuth chlorido salicylhydroxamato complex, [BiCl2(-Sha-1H)]∞, was investigated against a broad panel of bacteria, further highlighting the antibacterial properties of Bi-based compounds against Gram-positive and Gram-negative pathogenic and ...


Novel Improved Synthesis Of Hsp70 Inhibitor, Pifithrin-Μ. In Vitro Synergy Quantification Of Pifithrin-Μ Combined With Pt Drugs In Prostate And Colorectal Cancer Cells., Aoife M. Mckeon, Alan Egan, Jay Chandanshive, Helena Mcmahon, Darren M. Griffith Jul 2016

Novel Improved Synthesis Of Hsp70 Inhibitor, Pifithrin-Μ. In Vitro Synergy Quantification Of Pifithrin-Μ Combined With Pt Drugs In Prostate And Colorectal Cancer Cells., Aoife M. Mckeon, Alan Egan, Jay Chandanshive, Helena Mcmahon, Darren M. Griffith

Chemistry Articles

We describe a novel improved approach to the synthesis of the important and well-known heat shock protein 70 inhibitor (HSP70), pifithrin-μ, with corresponding and previously unreported characterisation. The first example of a combination study comprising HSP70 inhibitor pifithrin-μ and cisplatin or oxaliplatin is reported. We have determined, using the Chou-Talalay method, (i) moderate synergistic and synergistic effects in co-treating PC-3 prostate cancer cells with pifithrin-μ and cisplatin and (ii) significant synergistic effects including strong synergism in cotreating HT29 colorectal cancer cells with oxaliplatin and pifithrin-μ.


Azadipyrromethenes: From Traditional Dye Chemistry To Leading Edge Applications., Yuan Ge, Donal F. O'Shea Jul 2016

Azadipyrromethenes: From Traditional Dye Chemistry To Leading Edge Applications., Yuan Ge, Donal F. O'Shea

Chemistry Articles

Azadipyrromethenes were first described over 70 years ago as blue pigments, but now are rapidly emerging as a compound class with highly desirable near infrared photophysical properties. Since the turn of the century several routes to azadipyrromethenes have been developed and numerous post-synthesis derivatizations have allowed for their exploitation in both biological and material sciences. The relative ease of access to specifically designed derivatives is now allowing their use in multiple technological formats from real-time fluorescence imaging, to solar energy materials, to optoelectronic devices and many more. In this review we have highlighted the synthetic component of this story as ...


Novel Class Of Bi(Iii) Hydroxamato Complexes: Synthesis, Urease Inhibitory Activity And Activity Against H. Pylori., Donal M. Keogan, Brendan Twamley, Deirdre Fitzgerald-Hughes, Darren M. Griffith Jul 2016

Novel Class Of Bi(Iii) Hydroxamato Complexes: Synthesis, Urease Inhibitory Activity And Activity Against H. Pylori., Donal M. Keogan, Brendan Twamley, Deirdre Fitzgerald-Hughes, Darren M. Griffith

Chemistry Articles

Reaction of Bi(NO3)3 with benzohydroxamic acid (Bha) and salicylhydroxamic acid (Sha) gives the novel Bi(iii) complexes [Bi2(Bha-1H)2(μ-Bha-1H)2(η(2)-NO3)2] () and [Bi6(CH3OH)2(η(1)-NO3)2(η(2)-NO3)(OH2)2(Sha-1H)12](NO3)2 (). X-ray crystal structure of reveals two hydroxamato coordination modes; bidentate bridging (O, O') and bidentate non-bridging (O, O') and of reveals one coordination mode; bidentate bridging (O, O'). , specifically designed to and demonstrated to inhibit the activity of urease, exhibits excellent antibacterial activity against three strains of Helicobacter pylori with MIC ≥ 16 μg mL(-1).


Fabrication Of A Gma-Co-Edma Monolith In A 2.0 Mm I.D. Polypropylene Housing., Marcello Iacono, Damian Connolly, Andreas Heise Mar 2016

Fabrication Of A Gma-Co-Edma Monolith In A 2.0 Mm I.D. Polypropylene Housing., Marcello Iacono, Damian Connolly, Andreas Heise

Chemistry Articles

Polymers are interesting housing materials for the fabrication of inexpensive monolithic chromatography and solid phase extraction (SPE) devices. Challenges arise when polymeric monoliths are formed in non-conical, cylindrical tubes of larger diameter due to potential monolith detachment from the housing wall resulting in loss of separation performance and mechanical stability. Here, a two-step protocol is applied to ensure formation of robust homogeneous methacrylate monolith in polypropylene (PP) tubing with a diameter of 2.0 mm. Detailed Fourier-transform infrared (FTIR) spectroscopic analysis and Scanning Electron Microscopy (SEM) imaging confirm the successful pre-modification of the tubing wall with an anchoring layer of ...


Lysosome Triggered Near-Infrared Fluorescence Imaging Of Cellular Trafficking Processes In Real Time., Marco Grossi, Marina Morgunova, Shane Cheung, Dimitri Scholz, Emer Conroy, Marta Terrile, Angela Panarella, Jeremy C. Simpson, William M. Gallagher, Donal F. O'Shea Mar 2016

Lysosome Triggered Near-Infrared Fluorescence Imaging Of Cellular Trafficking Processes In Real Time., Marco Grossi, Marina Morgunova, Shane Cheung, Dimitri Scholz, Emer Conroy, Marta Terrile, Angela Panarella, Jeremy C. Simpson, William M. Gallagher, Donal F. O'Shea

Chemistry Articles

Bioresponsive NIR-fluorophores offer the possibility for continual visualization of dynamic cellular processes with added potential for direct translation to in vivo imaging. Here we show the design, synthesis and lysosome-responsive emission properties of a new NIR fluorophore. The NIR fluorescent probe design differs from typical amine functionalized lysosomotropic stains with off/on fluorescence switching controlled by a reversible phenol/phenolate interconversion. Emission from the probe is shown to be highly selective for the lysosomes in co-imaging experiments using a HeLa cell line expressing the lysosomal-associated membrane protein 1 fused to green fluorescent protein. The responsive probe is capable of real-time ...


A Novel Dual-Functioning Ruthenium(Ii)-Arene Complex Of An Anti-Microbial Ciprofloxacin Derivative - Anti-Proliferative And Anti-Microbial Activity., Ziga Ude, Isolda Romero-Canelón, Brendan Twamley, Deirdre Fitzgerald-Hughes, Peter J. Sadler, Celine Marmion Jan 2016

A Novel Dual-Functioning Ruthenium(Ii)-Arene Complex Of An Anti-Microbial Ciprofloxacin Derivative - Anti-Proliferative And Anti-Microbial Activity., Ziga Ude, Isolda Romero-Canelón, Brendan Twamley, Deirdre Fitzgerald-Hughes, Peter J. Sadler, Celine Marmion

Chemistry Articles

7-(4-(Decanoyl)piperazin-1-yl)-ciprofloxacin, CipA, (1) which is an analogue of the antibiotic ciprofloxacin, and its ruthenium(II) complex [Ru(η(6)-p-cymene)(CipA-H)Cl], (2) have been synthesised and the x-ray crystal structures of 1·1.3H2O·0.6CH3OH and 2·CH3OH·0.5H2O determined. The complex adopts a typical pseudo-octahedral 'piano-stool' geometry, with Ru(II) π-bonded to the p-cymene ring and σ-bonded to a chloride and two oxygen atoms of the chelated fluoroquinolone ligand. The complex is highly cytotoxic in the low μM range and is as potent as the clinical drug cisplatin against the human cancer ...


Stable Poly(Methacrylic Acid) Brush Decorated Silica Nano-Particles By Arget Atrp For Bioconjugation, Marcello Iacono, Andreas Heise Jan 2015

Stable Poly(Methacrylic Acid) Brush Decorated Silica Nano-Particles By Arget Atrp For Bioconjugation, Marcello Iacono, Andreas Heise

Chemistry Articles

The synthesis of polymer brush decorated silica nano-particles is demonstrated by activator regeneration by electron transfer atom transfer radical polymerization (ARGET ATRP) grafting of poly(tert-butyl methacrylate). ATRP initiator decorated silica nano-particles were obtained using a novel trimethylsiloxane derivatised ATRP initiator obtained by click chemistry. Comparison of de-grafted polymers with polymer obtained from a sacrificial initiator demonstrated good agreement up to 55% monomer conversion. Subsequent mild deprotection of the tert-butyl ester groups using phosphoric acid yielded highly colloidal and pH stable hydrophilic nano-particles comprising approximately 50% methacrylic acid groups. The successful bio-conjugation was achieved by immobilization of Horseradish Peroxidase to ...


Poly(Ethylene Glycol)-Based Backbones With High Peptide Loading Capacities., Aoife O'Connor, Jean-Noel Marsat, Annachiara Mitrugno, Tom Flahive, Niamh Moran, David Brayden, Marc Devocelle Oct 2014

Poly(Ethylene Glycol)-Based Backbones With High Peptide Loading Capacities., Aoife O'Connor, Jean-Noel Marsat, Annachiara Mitrugno, Tom Flahive, Niamh Moran, David Brayden, Marc Devocelle

Chemistry Articles

Polymer-peptide conjugates are a promising class of compounds, where polymers can be used to overcome some of the limitations associated with peptides intended for therapeutic and/or diagnostic applications. Linear polymers such as poly(ethylene glycol) can be conjugated through terminal moieties and have therefore limited loading capacities. In this research, functionalised linear poly(ethylene glycol)s are utilised for peptide conjugation, to increase their potential loading capacities. These poly(ethylene glycol) derivatives are conjugated to peptide sequences containing representative side-chain functionalised amino acids, using different conjugation chemistries, including copper-catalysed azide-alkyne cycloaddition, amide coupling and thiol-ene reactions. Conjugation of a ...


Computational Survey Of Peptides Derived From Disulphide-Bonded Protein Loops That May Serve As Mediators Of Protein-Protein Interactions., Fergal J. Duffy, Marc Devocelle, David R. Croucher, Denis C. Shields Sep 2014

Computational Survey Of Peptides Derived From Disulphide-Bonded Protein Loops That May Serve As Mediators Of Protein-Protein Interactions., Fergal J. Duffy, Marc Devocelle, David R. Croucher, Denis C. Shields

Chemistry Articles

BACKGROUND: Bioactive cyclic peptides derived from natural sources are well studied, particularly those derived from non-ribosomal synthetases in fungi or bacteria. Ribosomally synthesised bioactive disulphide-bonded loops represent a large, naturally enriched library of potential bioactive compounds, worthy of systematic investigation.

RESULTS: We examined the distribution of short cyclic loops on the surface of a large number of proteins, especially membrane or extracellular proteins. Available three-dimensional structures highlighted a number of disulphide-bonded loops responsible for the majority of the likely binding interactions in a variety of protein complexes, due to their location at protein-protein interfaces. We find that disulphide-bonded loops at ...


Bu4n(+) Alkoxide-Initiated/Autocatalytic Addition Reactions With Organotrimethylsilanes., Manas Das, Donal F. O'Shea Jun 2014

Bu4n(+) Alkoxide-Initiated/Autocatalytic Addition Reactions With Organotrimethylsilanes., Manas Das, Donal F. O'Shea

Chemistry Articles

The use of Me3SiO(-)/Bu4N(+) as a general activator of organotrimethylsilanes for addition reactions has been established. The broad scope of the method offers trimethylsilanes (including acetate, allyl, propargyl, benzyl, dithiane, heteroaryl, and aryl derivatives) as bench-stable organometallics that can be readily utilized as carbanion equivalents for synthesis. Reactions are achieved at rt without the requirement of specialized precautions that are commonplace for other organometallics.


Current And Potential Applications Of Bismuth-Based Drugs., Donal M. Keogan, Darren M. Griffith Jan 2014

Current And Potential Applications Of Bismuth-Based Drugs., Donal M. Keogan, Darren M. Griffith

Chemistry Articles

Bismuth compounds have been used extensively as medicines and in particular for the treatment of gastrointestinal ailments. In addition to bismuth's well known gastroprotective effects and efficacy in treating H. pylori infection it also has broad anti-microbial, anti-leishmanial and anti-cancer properties. Aspects of the biological chemistry of bismuth are discussed and biomolecular targets associated with bismuth treatment are highlighted. This review strives to provide the reader with an up to date account of bismuth-based drugs currently used to treat patients and discuss potential medicinal applications of bismuth drugs with reference to recent developments in the literature. Ultimately this review ...


Targeted Antimicrobial Peptides., Marc Devocelle Jan 2012

Targeted Antimicrobial Peptides., Marc Devocelle

Chemistry Articles

The existence of natural antimicrobial substances, contributing to the mechanisms of host defenses, has been recognized since the late nineteenth century. In 1963, the in vitro antibacterial activity of leukocyte extracts was attributed to basic proteins. Since the late 1980s, cationic peptides with antimicrobial properties have been subsequently identified in other host cells and tissues and in virtually every living species (Lehrer, 2004). The properties of these “Nature’s antibiotics” and their multiple functions in host defenses of multicellular organisms support the rationale of developing entirely novel peptide-based therapeutics harnessing the effector mechanisms of innate immunity (Hancock and Sahl, 2006 ...


In Vitro Activities Of Synthetic Host Defense Propeptides Processed By Neutrophil Elastase Against Cystic Fibrosis Pathogens., Stephane Desgranges, Florie Le Prieult, Alan Daly, Marian Brennan, Dilip K. Rai, Anusha P. Subasinghage, Chandralal M. Hewage, Sally-Ann Cryan, Catherine M. Greene, Noel G. Mcelvaney, Timothy P. Smyth, Deirdre Fitzgerald-Hughes, Hilary Humphreys, Marc Devocelle May 2011

In Vitro Activities Of Synthetic Host Defense Propeptides Processed By Neutrophil Elastase Against Cystic Fibrosis Pathogens., Stephane Desgranges, Florie Le Prieult, Alan Daly, Marian Brennan, Dilip K. Rai, Anusha P. Subasinghage, Chandralal M. Hewage, Sally-Ann Cryan, Catherine M. Greene, Noel G. Mcelvaney, Timothy P. Smyth, Deirdre Fitzgerald-Hughes, Hilary Humphreys, Marc Devocelle

Chemistry Articles

The antimicrobial and hemolytic activities of a host defense peptide can be controlled by its modification as a propeptide of reduced net charge, which can then be processed by neutrophil elastase, a serine protease involved in chronic airway inflammation and infections associated with cystic fibrosis.


A Novel Anti-Cancer Bifunctional Platinum Drug Candidate With Dual Dna Binding And Histone Deacetylase Inhibitory Activity., Darren Griffith, Maria P. Morgan, Celine J. Marmion Nov 2009

A Novel Anti-Cancer Bifunctional Platinum Drug Candidate With Dual Dna Binding And Histone Deacetylase Inhibitory Activity., Darren Griffith, Maria P. Morgan, Celine J. Marmion

Chemistry Articles

The successful design and synthesis of a novel multifunctional platinum drug candidate with DNA binding, histone deacetylase inhibitory activity and enhanced selectivity for cancer cells are described.