Structural Studies of Anti-cancer Drugs and Their Interactions with Nucleic Acids PDF Download

Author: Robert McKenna
Publisher:
ISBN:
Category :
Languages : en
Pages : 732

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Author: Stephen Neidle
Publisher:
ISBN:
Category : Antimitotic agents
Languages : en
Pages : 424

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Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 702

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Author: Stephen Neidle
Publisher: CRC Press
ISBN: 9780849377730
Category : Medical
Languages : en
Pages : 386

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This cutting-edge book surveys the current knowledge on the mode of action of the major classes of DNA-interactive antitumor agents, providing information that could be crucial for the discovery of new therapeutic substances. It is an important reference for molecular biologists, cancer researchers, biochemists, biophysicists, and pharmacologists.

Author: Astrid Sigel
Publisher: Walter de Gruyter GmbH & Co KG
ISBN: 3110469901
Category : Science
Languages : en
Pages : 631

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Book Description
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.

Author: Michael Waring
Publisher: Springer Science & Business Media
ISBN: 9780792389590
Category : Medical
Languages : en
Pages : 300

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Most of the anti-cancer drugs in use today were discovered by happy accident rather than design, yet the rational design of better anti-cancer drugs remains a cherished goal, and one of the most important challenges facing medical science. This book represents a compilation of views and progress reports which illustrate the diversity of approaches to the problem. Recent research has confirmed the belief that critical genetic changes are at work in cancer cells. The genome, then (DNA in biochemical terms), surely represents a critical target for specific chemotherapy of cancer, and several chapters address the issue of attacking DNA, gene targetting, and the like. Others deal with principles of rational design, exploitation of novel modalities and targets, or the nuts and bolts of antitumour drug testing. While no attempt has been made to provide a comprehensive coverage of this wide-ranging and vitally important subject, the present volume in the series will provide much food for thought.

Author: Neidle
Publisher: CRC Press
ISBN: 9780849377709
Category : Medical
Languages : en
Pages : 394

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Book Description
This cutting-edge book surveys the current knowledge on the mode of action of the major classes of DNA-interactive antitumor agents, providing information that could be crucial for the discovery of new therapeutic substances. It is an important reference for molecular biologists, cancer researchers, biochemists, biophysicists, and pharmacologists.

Author: Danzhou Yang
Publisher:
ISBN:
Category :
Languages : en
Pages :

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Chemotherapy with anticancer drugs is one of the main method of cancer treatment. The exploitation of the stereochemical interactions between anticancer drugs and DNA is of great importance for the ultimate clinical advances of cancer chemotherapy, which needs the detailed structural knowledge of DNA, drugs, and their interactions. Cisplatin is one of the most effecient and widely used anticancer drugs in the world. Extensive effort has been devoted to designing the new better anticancer platinum compounds. The structural studies on interactions of two anticancer platinum compounds, cisplatin and the third-generation bisplatinum compound 1,1/t,t, with DNA are described in this thesis. The structure of an intrastrand cisplatin-crosslinked didentate DNA duplex consisting of d(CCTG$rmsp*Gsp*$TCC) and its complement d(GGACCAGG) is determined by NMR spectroscopy. The refined duplex is unwound ($sim{-}21spcirc$) and kinked (${sim}58spcirc$) toward the major groove at the $rm Gsp*Gsp*$ site and the minor groove is significantly widened. The stability of the major intrastrand cisplatin-G$rmsp*pGsp*$ adduct has been studied and this intrastrand cisplatin-crosslinked adduct appears to be converted into an interstrand crosslink adduct. Three palindromic DNA oligonucleotides, each having a single intrastrand cisplatin crosslinked at GpG site, have also been studied by NMR spectroscopy. The structural consequence of the incorporation of the $rm Gsp*Gsp*$ lesions into palindromic sequences is dependent on the location of the lesion sites in the sequence. Such alternative structural distortions may be relevant in understanding the protein recognition of the cisplatin-induced lesions. A new anticancer bisplatinum compound 1,1/t,t exhibits excellent cytotoxicity towards cisplatin-resistant cancer cells. The structure of the interstrand adduct of 1,1/t,t with a palindromic DNA oligomer CATGCATG has been determined by NMR spectroscopy. Upon platination by 1,1/t,t, the DNA octamer forms a novel hairpin structure with the platinated G$sb4$ residue adopting a syn conformation and with the guanine base in the minor groove. Two such hairpins stack end-over-end and are linked together by the butanediamine tether to form a dumbbell structure. Such unusual structural distortion induced by the bisplatinum compound is completely different from that of the anticancer drug cisplatin-DNA adduct and may provide clues to explain the distinct biological activities of the two compounds. Anthracycline antibiotics are important anticancer intercalative drugs. The solution structures of anticancer anthracycline drugs aclacinomycin A and B, nogalamycin and disnogalamycin, complexed to a DNA hexamer have all been determined by high resolution NMR spectroscopy. Structural modification of DNA through covalent interactions have significant functional consequences and/or anticancer activities. Structural analysis of the C$sp2$-methyl-hypoxanthine:Cytosine base pair and O$sp6$-ethyl-Guanine:Cytosine base pair in B-DNA help understand their biological functions.

Author: Loutfy H. Madkour
Publisher: Academic Press
ISBN: 0128197781
Category : Science
Languages : en
Pages : 652

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Nucleic Acids as Gene Anticancer Drug Delivery Therapy highlights the most recent developments in cancer treatment using nucleic acids, nanoparticles and polymer nanoparticles for genomic nanocarriers as drug delivery, including promising opportunities for targeted and combination therapy. The development of a wide spectrum of nanoscale technologies is beginning to change the scientific landscape in terms of disease diagnosis, treatment, and prevention. This book presents the use of nanotechnology for medical applications, focusing on its use for anticancer drug delivery. Various intelligent drug delivery systems such as inorganic nanoparticles and polymer-based drug delivery are discussed. The use of smart drug delivery systems seems to be a promising approach for developing intelligent therapeutic systems for cancer immunotherapies and is discussed in detail along with nucleic acid-targeted drug delivery combination therapy for cancer. Nucleic Acids as Gene Anticancer Drug Delivery Therapy will be a useful reference for pharmaceutical scientists, pharmacologiests, and those involved in nanotechnology and cancer research. - Discusses intelligent drug delivery systems such as inorganic nanoparticles and polymer-based drug delivery - Contains a comprehensive comparison of various delivery systems, listing their advantages and limitations - Presents combination therapy as a new hope for enhancing current gene-based treatment efficacy

Author: Bernard Pullman
Publisher: Springer Science & Business Media
ISBN:
Category : Medical
Languages : en
Pages : 624

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Mutual Conformational Adaptation of Both Ligand and Receptor in Antitumor Drug-DNA Complexes.- DNA Drug Interactions studied with Polarized Light Spectroscopy: the DAPI Case.- Drug-DNA Recognition: Sequence Specificity of the DNA Minor Groove Binder Berenil.- Binding of Minor Groove Ligands to Short DNA Segments: Berenil Complexed with d(GCAATTGC)2 and d(GCTTAAGC)2.- The Sequence Specificity of Damage Caused by [125I]-Labelled Hoechst 33258 and UV/IodoHoechst 33258 in Intact Cells and in Cloned Sequences of Purified DNA which differ by a Small Number of Base Substitutions.- Structure and Dynamics of a [1:1] Drug-DNA Complex: Analysis of 2D NMR Data Using Molecular Mechanics and Molecular Dynamics Calculations.- Determination of Distamycin-A Binding Modes by NMR.- Molecular Mechanisms of DNA Sequence Recognition by Groove Binding Ligands: Biochemical and Biological Consequences.- Daunomycin Binding to DNA: from the Macroscopic to the Microscopic.- In Vitro Transcription Analysis of the Sequence Specificity of Reversible and Irreversible Complexes of Adriamycin with DNA.- Quantitative Footprinting Analysis of the Actiomycin D-DNA Interaction.- Structural Requirements for DNA Topoisomerase II Inhibition by Anthracyclines.- Thermodynamic Studies of Amsacrine Antitumor Agents with Nucleic Acids.- Kinetic and Equilibrium Binding Studies of a Series of Intercalating Agents that Bind by Threading a Sidechain Through the DNA Helix.- Aminoacyl-Anthraquinones: DNA-Binding and Sequence Specificity.- The Molecular Basis of Specific Recognition Between Echinomycin and DNA.- Bis-Pyrrolecarboxamides Linked to Intercalating Chromophore Oxazolopyridocarbazole (OPC): Properties Related to the Selective Binding to DNA at Rich Sequences.- Parallel-Stranded Nucleic Acids and their Interaction with Intercalating and Groove Binding Drugs.- Design of Bifunctional Nucleic Acid Ligands.- Sequence-Specific Recognition and CLeavage of Duplex DNA by Derivatized Oligonucleotides.- Bis(Platinum) Complexes. Chemistry, Antitumor Activity and DNA-Binding.- Interaction of Calicheamicin with DNA.- The Effects of Ligand Structure on Binding Mode and Specificity in the Interaction of Unfused Aromatic Cations with DNA.- Modulation of Protein-DNA Interactions by Intercalating and Nonintercalating Agents.- Antitumor Antibiotics Endowed with DNA Sequence Specificity.- Cationic Porphyrin-DNA Complexes: Specificity of Binding Modes.- Complementary Studies on Sequence Specificity in DNA-Antitumor Drugs Interactions.- Uranyl Photofootpring. DNA Structural Changes upon Binding of Mithramycin.- Characteristics of Noncovalent and Covalent Interactions of (+) and (-) Anti-Benzo[a]pyrene Diol Epoxide Stereoisomers of Different Biological Activities with DNA.- Aflatoxin-DNA Binding and the Characterization of Aflatoxin B1-Oligodeoxynucleotide Adducts by 1H NMR Spectroscopy.- Sequence Specific Isotope Effects on the Cleavage of DNA by Radical-Generating Drugs.- Quinolone-DNA Interaction: How a Small Drug Molecule Acquires High DNA Binding Affinity and Specificity.- Mechanisms of DNA Sequence Selective Modifications by Alkylating Agents.- Contrasting Mechanisms for the Sequence Recognition of DNA by(+)- and (-)-CC-1065.- Course of Recognition and Covalent Reactions Between Mitomycin C and DNA: Sequence Selectivity of a Cross-Linking Drug.- Triplex Forming Oligonucleotide Reagents: Rationalization of DNA Site Selectivity and Application in a Pharmaceutical Context.- Experimental Proofs of a Drug's DNA Specificity.