Kooperativer Bibliotheksverbund

Language: English

In: Journal of Biological Inorganic Chemistry, 2015, Vol.20(5), pp.841-853

Description: The structure-activity relationships of chiral 1,2-diaminophenylalkane platinum(II) anticancer derivatives are studied, including interactions with telomeric- and genomic-like DNA sequences, the pKa of their diaqua species, structural properties obtained from DFT calculations and resonant X-ray emission...

Keywords: Natural Sciences ; Biological Sciences ; Biochemistry And Molecular Biology ; Naturvetenskap ; Biologiska Vetenskaper ; Biokemi Och Molekylärbiologi ; Cancer ; Platinum ; G-Quadruplex ; Conceptual Dft ; Rxes

ISSN: 0949-8257

E-ISSN: 14321327

DOI: 10.1007/s00775-015-1270-6

URL: View source record

In: Analyst, 2016, Vol.141(4), pp.1226-1232

Description: Platinum-based drugs are commonly used in cancer treatment. The biological activity of a metallodrug is obviously closely related to its chemical and stereochemical characteristics. An overlooked aspect is the effect of the ligand to the electronic structure of the metal atom (coordinated atom). We report herein a Resonant X-ray Emission Spectroscopy (RXES) study on the chemical speciation of chiral platinum complexes in which diastereomers are distinguished on the basis of their metal electronic configuration. This demonstrates RXES high chemical speciation capabilities, a necessary property to further investigate the reactivity of the Pt atom towards nucleophiles or bionucleophiles, and an important complement the previously reported RXES abilities, namely that it can be employed for in situ studies at physiological concentrations.

Keywords: Spectrometry, X-Ray Emission ; Antineoplastic Agents -- Chemistry ; Organoplatinum Compounds -- Chemistry;

ISSN: 0003-2654

E-ISSN: 1364-5528

DOI: 10.1039/c5an02490k

Language: English

In: JBIC Journal of Biological Inorganic Chemistry, 2015, Vol.20(5), p.841(13)

Description: Byline: Gilles Berger (1), Luca Fusaro (2), Michel Luhmer (2), Joanna Czapla-Masztafiak (3), Ewelina Lipiec (3), Jakub Szlachetko (4,5), Yves Kayser (4), Daniel L. A. Fernandes (6), Jacinto Sa (6,7), Francois Dufrasne (1), Sophie Bombard (8) Keywords: Cancer; Platinum; G-quadruplex; Conceptual DFT; RXES Abstract: The structure--activity relationships of chiral 1,2-diaminophenylalkane platinum(II) anticancer derivatives are studied, including interactions with telomeric- and genomic-like DNA sequences, the pKa of their diaqua species, structural properties obtained from DFT calculations and resonant X-ray emission spectroscopy. The binding modes of the compounds to telomeric sequences were elucidated, showing no major differences with conventional cis-platinum(II) complexes like cisplatin, supporting that the cis-square planar geometry governs the binding of small Pt(II) complexes to G4 structures. Double-stranded DNA platination kinetics and acid--base constants of the diaqua species of the compounds were measured and compared, highlighting a strong steric dependence of the DNA-binding kinetics, but independent to stereoisomerism. Structural features of the compounds are discussed on the basis of dispersion-corrected DFT, showing that the most active series presents conformers for which the platinum atom is well devoid of steric hindrance. If reactivity indices derived from conceptual DFT do not show evidences for different reactivity between the compounds, RXES experiments provide new insight into the availability of platinum orbitals for binding to nucleophiles. Author Affiliation: (1) Laboratoire de Chimie Pharmaceutique Organique, Universite Libre de Bruxelles, Campus Plaine CP205/5, Bd du Triomphe, 1050, Brussels, Belgium (2) Laboratoire de Resonance Magnetique Nucleaire Haute Resolution, Universite Libre de Bruxelles (ULB), Avenue F.D. Roosevelt 50, CP160/08, 1050, Brussels, Belgium (3) The Henryk Niewodniczanski Institute of Nuclear Physics, Polish Academy of Sciences, Krakow, Poland (4) Paul Scherrer Institute (PSI), Villigen, Switzerland (5) Institute of Physics, Jan Kochanowski University in Kielce, Kielce, Poland (6) Angstrom Laboratory, Department of Chemistry, Uppsala University, Uppsala, Sweden (7) Institute of Physical Chemistry, Polish Academy of Sciences, Warsaw, Poland (8) Homeostasie Cellulaire et Cancer, UMR-S INSERM 1007, Universite Paris Descartes, 45 rue des Saint-Peres, 75006, Paris, France Article History: Registration Date: 07/05/2015 Received Date: 02/04/2015 Accepted Date: 03/05/2015 Online Date: 16/05/2015 Article note: Electronic supplementary material The online version of this article (doi: 10.1007/s00775-015-1270-6) contains supplementary material, which is available to authorized users.

Keywords: Nuclear Physics ; Cancer Treatment ; Stereoisomers

ISSN: 0949-8257

Source: Cengage Learning, Inc.

Language: English

In: Drug Discovery Today: Technologies, September 2015, Vol.16, pp.1-6

Description: This review presents a new application of Resonant X-ray Emission Spectroscopy (RXES) to study the mechanism of action of metal containing anticancer derivatives and in particular platinum and . The technique is an example of a photon-in photon-out X-ray spectroscopic approach, which enables chemical speciation of drugs to be determined and therefore to derive action mechanisms, and to determine drug binding rates under physiological conditions and therapeutic concentrations. This is made feasible due to the atomic specificity and high penetration depth of RXES. The review presents examples of the three main types of information that can be obtained by RXES and establishes an experimental protocol to perfect the measurements within cells.

Keywords: Pharmacy, Therapeutics, & Pharmacology

ISSN: 1740-6749

E-ISSN: 1740-6749

DOI: 10.1016/j.ddtec.2015.07.001

URL: View record in ScienceDirect (Access to full text may be restricted)

Language: English

In: Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry, July 2015, Vol.20(5), pp.841-53

Description: The structure-activity relationships of chiral 1,2-diaminophenylalkane platinum(II) anticancer derivatives are studied, including interactions with telomeric- and genomic-like DNA sequences, the pKa of their diaqua species, structural properties obtained from DFT calculations and resonant X-ray emission spectroscopy. The binding modes of the compounds to telomeric sequences were elucidated, showing no major differences with conventional cis-platinum(II) complexes like cisplatin, supporting that the cis-square planar geometry governs the binding of small Pt(II) complexes to G4 structures. Double-stranded DNA platination kinetics and acid-base constants of the diaqua species of the compounds were measured and compared, highlighting a strong steric dependence of the DNA-binding kinetics, but independent to stereoisomerism. Structural features of the compounds are discussed on the basis of dispersion-corrected DFT, showing that the most active series presents conformers for which the platinum atom is well devoid of steric hindrance. If reactivity indices derived from conceptual DFT do not show evidences for different reactivity between the compounds, RXES experiments provide new insight into the availability of platinum orbitals for binding to nucleophiles.

Keywords: Antineoplastic Agents -- Chemistry ; DNA, Neoplasm -- Drug Effects ; Hydrocarbons, Chlorinated -- Pharmacology ; Organoplatinum Compounds -- Chemistry

ISSN: 09498257

E-ISSN: 1432-1327

DOI: 10.1007/s00775-015-1270-6

Source: MEDLINE/PubMed (U.S. National Library of Medicine)

URL: View this record in MEDLINE/PubMed