Download or read book Structure activity Relationships of Ruthenium II Polypyridyl Complexes with Redox active Intercalating Ligands written by Eugenia Soyo Narh and published by . This book was released on 2016 with total page 124 pages. Available in PDF, EPUB and Kindle. Book excerpt: The investigation and development of transition metal complexes as cancer chemotherapeutics has gained a lot of interest in the past few decades and has become a promising area of research. Metal complexes of platinum and ruthenium in particular that have demonstrated success as anticancer drugs or are under exploration currently for clinical use are highlighted in Chapter 1. Chapter 2 describes studies undertaken to understand the neurotoxicity of ruthenium(II) polypyridyl complexes (RPCs), including toxicity in mice and inhibition of the enzyme acetylcholinesterase (AChE), as previous work by Dwyer demonstrated that RPCs could be acutely toxic in mice, presumably due to their inhibition of AChE. Several ruthenium complexes were screened for their enzyme inhibitory potency which was correlated to their structural properties including size, charge, and lipophilicity. In addition, the inhibitory activity of the compounds was correlated to their animal toxicity data so as to understand the potential mode of action of the RPCs in vivo. Chapter 3 describes the synthesis of a series of novel ruthenium(II) polypyridyl complexes and their characterization. These complexes were prepared in an effort to tune the reduction potential of the redox-active intercalating ligand (RAIL) to potentials slightly above and below those observed for the Ru-tatpp complexes. The redox activity of ruthenium-tatpp complexes appears to be responsible for their DNA cleavage activity and these analogues, with slightly different reduction potentials, should give us additional insight into the activity of this class of RPCs. In Chapter 4, the electrochemical properties of the RPCs were measured and correlated with their ability to cause DNA cleavage under reducing conditions with GSH. Complexes with reduction potentials less (more positive) than the redox couple of GSH/GSSG were shown to efficiently cleave DNA. However complexes with higher reduction potentials than the biological reducing agent were not observed to cleave DNA under the same conditions. Cytotoxicity screening of these complexes in human non-small cell lung carcinoma cell lines (NSCLC -- H358 and HOP-62) and breast adenocarcinoma cell line (MCF-7), as well as the non-malignant cell line (MCF-10) was performed and described in Chapter 4.

Download or read book Ruthenium Complexes written by Alvin A. Holder and published by John Wiley & Sons. This book was released on 2018-02-27 with total page 344 pages. Available in PDF, EPUB and Kindle. Book excerpt: Edited by a team of highly respected researchers combining their expertise in chemistry, physics, and medicine, this book focuses on the use of rutheniumcontaining complexes in artificial photosynthesis and medicine. Following a brief introduction to the basic coordination chemistry of ruthenium complexes and their synthesis in section one, as well as their photophysical and photochemical properties, the authors discuss in detail the major concepts of artificial photosynthesis and mechanisms of hydrogen production and water oxidation with ruthenium in section two. The third section of the text covers biological properties and important medical applications of ruthenium complexes as therapeutic agents or in diagnostic imaging. Aimed at stimulating research in this active field, this is an invaluable information source for researchers in academia, health research institutes and governmental departments working in the field of organometallic chemistry, green and sustainable chemistry as well as medicine/drug discovery, while equally serving as a useful reference also for scientists in industry.

Download or read book Investigation of Ruthenium II Polypyridyl Dimers as Potential Chemotherapeutic Agents written by Thamara K. Janaratne and published by . This book was released on 2006 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The exploration of transition metal complexes as chemotherapeutic agents is still a relatively unexplored but promising area of research. Chapter 1 highlights the most successful anticancer drugs and potential drugs based on metal complexes, with an emphasis of platinum and ruthenium complexes. In Chapter 2, the biological activity of a series of novel ruthenium dimers is investigated with special attention given to evaluating their potential as anticancer chemotherapeutic agents. A partial list of the compound prepared includes: [Ru(bpy)(CO)2}2tpphz]4+ (74+), [Ru(bpy)(CH3CN)2}2 tpphz]4+(84+), [Ru(bpy)(C 2O4)}2tpphz] (9), [Ru(bpy)(CO)(Cl)} 2tpphz]2+ (102+), [(bpy) 2Ru(tpphz)Ru(bpy)2]4+ (11 4+), [(phen)2Ru(tpphz)Ru(phen)2] 4+ (124+), [(phen)2Ru(tatpp)Ru(phen) 2]4+ (Pp4+), [(phen) 2Ru(tatpq)Ru(phen)2]4+ (Qp 4+), [(bpy)2Ru(tatpp)Ru(bpy)2]4+ (Pb4+) and [(bpy)2Ru(tatpq)Ru(bpy) 2]4+ (Qb4+). Systematic changes in functions, such as overall charge (+4, +2, 0), the presence or absence of labile ligands, long and short bridging ligands between metal centers, and redox inactive (tpphz) and active (tatpp and tatpq) ligands allowed us to complete a structure-activity evaluation of this class of potential anticancer drugs. Most promising were the cationic dimers containing long, redox active bridging ligands, Pp4, P b4+, Qp4+ and Qb4+, which showed very high DNA binding constants (Kb = 107 to 109 M-1) and good cytotoxicity against cancer cell lines (NSCLC). Animal toxicity studies (mice) showed most cationic complexes to be acutely toxic at relatively lower doses. However, the cationic dimers containing the long tatpp or tatpq bridging ligands were well tolerated in mice with maximum tolerable doses in the range of 67-167 mg/kg for Pp 4+ and 6.7-17 mg/kg for Qp4+ as the chloride salts. These promising results led to a study of the antitumor activity of Pp4+ and Qp 4+ in vivo using a mouse melanoma model. Excitingly, complex Pp4+ seems to inhibit tumor growth in vivo although a little difference in survival times was observed. Nonetheless, the results are promising in that this was an initial screen in which numerous parameters including dosage, frequency of treatment, tumor type, etc., remains unoptimized. The ability of these complexes to damage DNA was evaluated in Chapter 3 by using a plasmid DNA assay that shows if a complex can induce single or double-strand cuts in the DNA molecule. None of the complexes causes any cleavage reactions unless an external reductant is added. However, upon addition of a common biological reductant (glutathione, dithiothritol or ascorbic acid), complex Pp4+ and Qp 4+ could be shown to induce single-strand cuts. Importantly, the DNA cleaving ability of Pp4+ is potentiated under anaerobic conditions, showing that the cleavage is not via O2 activation processes. Further studies established that complex P p4+ is doubly reduced under the assay conditions and the doubly reduced product, denoted H2Pp 4+, is the cleavage agent. As this species is oxygen sensitive and readily reoxidized to Pp4+ upon exposure to air, the [O2] 'regulates' the nuclease activity by controlling [H2Pp4+]. The ability of the ruthenium complexes to inhibit or poison topoisomerase I and II was evaluated and is reported in Chapter 4. The intercalating complexes showed the most significant topoisomerase I and II inhibition with complex Pp4+ standing out again for its potent biological activity.

Download or read book Ruthenium II Polypyridyl Complexes as Potential Anticancer Drugs written by Yanling Chen and published by . This book was released on 2013 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Research on biological activities of ruthenium polypyridyl complexes (RPCs) continues to attract interest as these complexes have shown promising anticancer activity both in vitro and in vivo.1−3 The mononuclear RPC, [(phen)2Ru(tatpp)]2+ (MP) and related dinuclear complex [(phen)2Ru(tatpp)Ru(phen)2]4+ (P) have been shown to both intercalate with DNA and shown potentiated DNA cleavage under anaerobic and reducing conditions4−5, as well as shown good selectivity and cytotoxicity towards malignant cell lines in vitro and tumors in vivo.5 Both complexes contain the redox-active tatpp ligand which is thought to be an essential component for the observed biological activities. This thesis is focused on developing improvements to the stereoselective syntheses of the chiral complexes, [delta][delta]-P and [delta]-MP. It is also investigated the synthesis of a new analogue [(phen)2Ru(tadbp)]2+ (B) and its chiral form [delta]-B which contains a modified tatpp ligand that is only capable of binding one Ru ion. Moreover this thesis explores the ability of these large complexes to traverse the cell membranes and get into cells and cell nuclei by isolating treated cells and nuclei and determining their ruthenium content by graphite furnace atomic absorption method (GFAAS). The GFAAS data show that the two examined complexes [delta][delta]-P and [delta]-MP are able to quickly penetrate into cancer cells (H-358) and concentrate in nuclei, which is postulated due to their high binding affinity to DNA.

Download or read book Increasing Lipophilicity of Redox Active Ruthenium Complexes as a Means to Enhance Cytotoxicity and Reduce Animal Toxicity written by Nagham Alatrash and published by . This book was released on 2012 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The dinuclear and monomeric ruthenium(II) polypyridyl complexes [(phen)2Ru(tatpp)Ru(phen)2]Cl4 (P) and monomer [(phen)2Ru(tatpp)]Cl2 (MP) are promising candidates for anticancer drug development in terms of the observed anti-tumor activity in mouse models. These complexes contain the redox-active tatpp bridging ligand which seems to be the critical component for biological activity. Ruthenium complexes containing the tatpp ligand have been shown to cleave DNA with an inverse dependence on the [O2], exhibit selective and good cytotoxicity towards a number of cultured malignant cell lines, and have tolerable acute toxicity in mice. Significantly, the animal toxicity of P and MP is significantly less than simple ruthenium polypyridyl complexes, such as [Ru(1,10-phenanthroline)3]2+ which may be due to the enhanced lipophilicity of these complexes. This thesis is a direct test of the following hypothesis. We postulate that by increasing the lipophilicity of P and MP we can further mollify their acute toxicity and enhance their cytotoxicity towards malignant cancer cells. Chapters 1 and 2 of this thesis develop this hypothesis in terms of a review of the prior literature and our synthetic approach to construct such complexes. In Chapter 2, the details of the synthesis and characterization of four new lipophilic ruthenium-tatpp complexes based on the P and MP structures. These are (Ph2phen)2Ru(tatpp)Ru(Ph2phen)2][PF6]4 (PPh2), (Ph2phen, 4,7-diphenyl1-1,10-phenanthroline), [(Me4phen)2Ru(tatpp)Ru(Me4phen)2][PF6]4 (PMe4), (Me4phen, 3,4,7,8 tetramethyl-1,10-phenanthroline), [(Me4phen)2Ru(tatpp)][PF6]2 (MPMe4), [(Ph2phen)2Ru(tatpp)][PF6]2 (MPPh2). All of these can be metathesized to their chloride salt, which is the preferred form for water solubility and biological testing. Chapter 3 presents the effect of these structural changes on the biological activity of the novel complexes in terms of the maximum tolerable dose (MTD) observed in mice, the IC50 values against malignant cell line, H358, and the ability of these complexes to cleave DNA, in vitro. In order to quantify the increase in lipophilicity, the partition coefficients (log P) were determined for the ruthenium complexes via the shake-flask method in PBS at pH 7.4 and octanol as well as in deionized water and octanol. It was found that the lipophilicity of these complexes increased as the lipophilic ancillary ligands changes from phen to Ph2phen and Me4phen ligands. The ability of these complexes to cleave DNA was maintained even with these ligand modifications. The cytotoxicity study against H358 cell line have revealed that the most promising activity was shown by PMe4 and PPh2 with an IC50 value of about 10 [mu]M. The lipophilic ruthenium complexes PPh2, PMe4, MPPh2, MPMe4 showed no acute animal toxicity in a screen of the MTD in Balb/c mice with doses up to 80 mg drug/Kg mouse.

Download or read book Design of Ruthenium Anticancer Drugs written by Anna Catharina Genovefa Hotze and published by . This book was released on 2003 with total page 177 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Synthesis and Electronic Structure Investigation of Ruthenium Complexes Containing Novel Redox active Ligands written by Fabian Ehret and published by . This book was released on 2014 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Ruthenium Polypyridyl Complexes with Anticancer Properties written by Eva Corral Simón and published by . This book was released on 2007 with total page 144 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Intraconversion of Redox Active Sulfur Bound Ligands in Polypyridyl Ruthenium Complexes written by Michael Gary Seamans and published by . This book was released on 2001 with total page 148 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Cisplatin written by Bernhard Lippert and published by John Wiley & Sons. This book was released on 1999 with total page 628 pages. Available in PDF, EPUB and Kindle. Book excerpt: 30 years after its discovery as an antitumor agent, cisplatin represents today one of the most successful drugs in chemotherapy. This book is intended to reminisce this event, to take inventory, and to point out new lines of development in this field. Divided in 6 sections and 22 chapters, the book provides an up-to-date account on topics such as - the chemistry and biochemistry of cisplatin, - the clinical status of Pt anticancer drugs, - the impact of cisplatin on inorganic and coordination chemistry, - new developments in drug design, testing and delivery. It also includes a chapter describing the historical development of the discovery of cisplatin. The ultimate question - How does cisplatin kill a cell? - is yet to be answered, but there are now new links suggesting how Pt binding to DNA may trigger a cascade of cellular reactions that eventually result in apoptosis. p53 and a series of damage recognition proteins of the HMG-domain family appear to be involved. The book addresses the problem of mutagenicity of Pt drugs and raises the question of the possible relevance of the minor DNA adducts, e.g. of interstrand cross-links, and the possible use of trans-(NH3)2Pt(II)-modified oligonucleotides in antisense and antigene strategies. Our present understanding of reactions of cisplatin with DNA is based upon numerous model studies (from isolated model nucleobases to short DNA fragments) and application of a large body of spectroscopic and other physico-chemical techniques. Thanks to these efforts there is presently no other metal ion whose reactions with nucleic acids are better understood than Pt. In a series of chapters, basic studies on the interactions of Pt electrophiles with nucleobases, oligonucleotides, DNA, amino acids, peptides and proteins are reported, which use, among others, sophisticated NMR techniques or X-ray crystallography, to get remarkable understanding of details on such reactions. Reactivity of cisplatin, once bound to DNA and formerly believed to be inert enough to stay, is an emerging phenomenon. It has (not yet) widely been studied but is potentially extremely important. Medicinal bioinorganic chemistry - the role of metal compounds in medicine - has received an enormous boost from cisplatin, and so has bioinorganic chemistry as a whole. There is hardly a better example than cisplatin to demonstrate what bioinorganic chemistry is all about: The marriage between classic inorganic (coordination) chemistry and the other life sciences - medicine, pharmacy, biology, biochemistry. Cisplatin has left its mark also on areas that are generally considered largely inorganic. The subject of mixed-valance Pt compounds is an example: From the sleeping beauty it made its way to the headlines of scientific journals, thanks to a class of novel Pt antitumor agents, the so-called "platinum pyrimidine blues". In the aftermath diplatinum (III) compounds were recognized and studies in large numbers, and now an organometalic chemistry of these diplatinum (III) species is beginning to emerge. The final section of the book is concerned with new developments such as novel di- and trinuclear Pt(II) drugs with DNA binding properties different from those of cisplatin, with orally active Pt(IV) drugs which are presently in clinical studies, and with attempts to modify combinatorial chemistry in such a way that it may become applicable to fast screening of Pt antitumor drugs. The potential of including computational methods in solving questions of Pt-DNA interactions is critically dealt with in the concluding chapter.

Download or read book Nucleic Acids written by Victor A. Bloomfield and published by Sterling Publishing Company. This book was released on 2000-04-17 with total page 854 pages. Available in PDF, EPUB and Kindle. Book excerpt: Providing a comprehensive account of the structures and physical chemistry properties of nucleic acids, with special emphasis on biological function, this text has been organized to meet the needs of those who have only a basic understanding of physical chemistry and molecular biology.

Download or read book Inorganic Chemical Biology written by Gilles Gasser and published by John Wiley & Sons. This book was released on 2014-06-23 with total page 437 pages. Available in PDF, EPUB and Kindle. Book excerpt: Understanding, identifying and influencing the biological systems are the primary objectives of chemical biology. From this perspective, metal complexes have always been of great assistance to chemical biologists, for example, in structural identification and purification of essential biomolecules, for visualizing cellular organelles or to inhibit specific enzymes. This inorganic side of chemical biology, which continues to receive considerable attention, is referred to as inorganic chemical biology. Inorganic Chemical Biology: Principles, Techniques and Applications provides a comprehensive overview of the current and emerging role of metal complexes in chemical biology. Throughout all of the chapters there is a strong emphasis on fundamental theoretical chemistry and experiments that have been carried out in living cells or organisms. Outlooks for the future applications of metal complexes in chemical biology are also discussed. Topics covered include: • Metal complexes as tools for structural biology • IMAC, AAS, XRF and MS as detection techniques for metals in chemical biology • Cell and organism imaging and probing DNA using metal and metal carbonyl complexes • Detection of metal ions, anions and small molecules using metal complexes • Photo-release of metal ions in living cells • Metal complexes as enzyme inhibitors and catalysts in living cells Written by a team of international experts, Inorganic Chemical Biology: Principles, Techniques and Applications is a must-have for bioinorganic, bioorganometallic and medicinal chemists as well as chemical biologists working in both academia and industry.

Download or read book Metallo Drugs Development and Action of Anticancer Agents written by Astrid Sigel and published by Walter de Gruyter GmbH & Co KG. This book was released on 2018-02-05 with total page 588 pages. Available in PDF, EPUB and Kindle. Book excerpt: Volume 18, entitled Metallo-Drugs: Development and Action of Anticancer Agents of the series Metal Ions in Life Sciences centers on biological, medicinal inorganic chemistry. The serendipitous discovery of the antitumor activity of cis-diamminodichloroplatinum(II) (cisplatin) by Barnett Rosenberg in the 1960s is a landmark in metallodrug-based chemotherapy. The success of cisplatin in the clinic, followed by oxaliplatin and carboplatin, along with their drawbacks relating mainly to resistance development and severe toxicity, initiated research on polynuclear platinum complexes and on Pt(IV) complexes as prodrugs. Furthermore, the indicated shortcomings led to the exploration of other transition and main group metal ions, among them Ru(II/III), Au(I/III), Ti(IV), V(IV/V), and Ga(III) including also the essential metal ions Fe(II/III), Cu(I/II), and Zn(II). Ionic as well as covalent and non-covalent interactions between structurally very different complexes and biomolecules like nucleic acids, proteins, and carbohydrates are studied and discussed with regard to their possible anticancer actions. Hence, MILS-18 summarizes the research at the forefront of medicinal inorganic chemistry, including studies on the next-generation, tailor-made anticancer drugs. All this and more is treated in an authoritative and timely manner in the 17 stimulating chapters of this book, written by 39 internationally recognized experts from 10 nations (from the US via Europe to China and Australia). The impact of this vibrant research area is manifested by more than 2700 references, nearly 150 illustrations (more than half in color) and several comprehensive tables. Metallo-Drugs: Development and Action of Anticancer Agents is an essential resource for scientists working in the wide range from enzymology, material sciences, analytical, organic, and inorganic biochemistry all the way through to medicine including the clinic ... not forgetting that it also provides excellent information for teaching.

Download or read book Chemical Aspects of Photodynamic Therapy written by Raymond Bonnett and published by CRC Press. This book was released on 2000-08-07 with total page 322 pages. Available in PDF, EPUB and Kindle. Book excerpt: Photodynamic therapy (PDT) is a ground breaking medical technique which uses lasers to activate light-sensitive chemicals to treat cancer and other diseases without resorting to surgery. For the first time, Chemical Aspects of Photodynamic Therapy introduces in an accessible way the physics, chemistry and biology behind the technique. This highly a

Download or read book Unconventional Anticancer Metallodrugs and Strategies to Improve their Pharmacological Profile written by Maria Contel and published by MDPI. This book was released on 2019-10-01 with total page 204 pages. Available in PDF, EPUB and Kindle. Book excerpt: For the past 40 years, metal-based drugs have been widely used for the treatment of cancer. Cisplatin and follow-up drugs carboplatin (ParaplatinTM) and oxaliplatin (EloxatinTM) have been the gold standard for metallodrugs in clinical settings as antineoplastic agents. While effective, these drugs (either alone or in combination therapy) have faced a number of clinical challenges resulting from their limited spectrum of activity, high toxicity leading to significant side effects, resistance, poor water solubility, low bioavailability and short circulating time. In the past 10 years, various unconventional non-platinum metal-based agents have emerged as a potential alternative for cancer treatment. These compounds are highly effective and selective in cancers resistant to cisplatin and other chemotherapeutic agents. Research in this area has recently exploded with a relevant number of patents and clinical trials, in addition to reports in scientific journals. Furthermore, in parallel to the synthesis of coordination and organometallic compounds comprising many different metals and unconventional platinum-based derivatives, researchers are focused on optimizing mechanistic and pharmacological features of promising drug candidates. This Special Issue aims to highlight the latest advances in anticancer metallodrugs with a focus on unconventional anticancer agents, as well as novel activation, targeting and delivery strategies aimed at improving their pharmacological profile.

Download or read book Electrogenerated Chemiluminescence written by Allen J. Bard and published by CRC Press. This book was released on 2004-07-20 with total page 707 pages. Available in PDF, EPUB and Kindle. Book excerpt: The first source on this expanding analytical science, this reference explores advances in the instrumentation, design, and application of techniques with electrogenerated chemiluminescence (ECL), examining the use and impact of ECL-based assays in clinical diagnostics, life science research, environmental testing, food and water evaluation, and th

Download or read book Photofunctional Transition Metal Complexes written by Vivian W. W. Yam and published by Structure and Bonding. This book was released on 2007-06-25 with total page 280 pages. Available in PDF, EPUB and Kindle. Book excerpt: With contributions by numerous experts