Synthesis, structural analysis and anticonvulsant activity of a ternary Cu(II) mononuclear complex containing 1,10-phenanthroline and the leading antiepileptic drug valproic acid

Autor: John R. J. Sorenson, Alain Tomas, Maité Sylla-Iyarreta Veitía, Yves Frapart, Françoise Dumas, Georges Morgant
Přispěvatelé: Biomolécules : Conception, Isolement, Synthèse (BioCIS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Université de Cergy Pontoise (UCP), Université Paris-Seine-Université Paris-Seine, Service de Biochimie et de Biologie Moléculaire [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de cristallographie et RMN biologiques (LCRB - UMR 8015), Laboratoire de cristallochimie Bioinorganique, Université Paris-Sud - Paris 11 (UP11), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Université Paris Descartes - Paris 5 (UPD5) - Centre National de la Recherche Scientifique (CNRS)
Rok vydání: 2009
Předmět:
Male
Stereochemistry
[CHIM.THER] Chemical Sciences/Medicinal Chemistry
Phenanthroline
medicine.medical_treatment
chemistry.chemical_element
[CHIM.THER]Chemical Sciences/Medicinal Chemistry
Crystal structure
Crystallography
X-Ray
010402 general chemistry
01 natural sciences
Biochemistry
Medicinal chemistry
law.invention
Mice
chemistry.chemical_compound
Seizures
law
Copper(II) complex
Organometallic Compounds
medicine
Animals
Chelation
Electron paramagnetic resonance
Ternary complex
ComputingMilieux_MISCELLANEOUS
Valproic Acid
Molecular Structure
[CHIM.ORGA]Chemical Sciences/Organic chemistry
010405 organic chemistry
Chemistry
Electron Spin Resonance Spectroscopy
Anticonvulsant properties
General Medicine
[CHIM.ORGA] Chemical Sciences/Organic chemistry
Copper
Rats
0104 chemical sciences
Slipped π–π Stacking
Anticonvulsant
Central nervous system
Anticonvulsants
Phenanthrolines
medicine.drug
Zdroj: Biochimie
Biochimie, Elsevier, 2009, 91 (10), pp.1286-1293. ⟨10.1016/j.biochi.2009.06.015⟩
Biochimie, Elsevier, 2009
ISSN: 0300-9084
DOI: 10.1016/j.biochi.2009.06.015
Popis: The synthesis and characterization of the binary complex of copper(II) with the antiepileptic drug valproic acid sodium salt (Valp) and the related ternary complex with 1,10-phenanthroline (phen) are reported, as well as the anticonvulsant properties of the latter. The characterization was carried out by means of elemental analyses, infrared (IR), UV-visible (UV-vis) spectrophotometry and Electron Paramagnetic Resonance (EPR). The X-ray crystal structure of the mononuclear complex bis(2-propylpentanoate)(1,10-phenanthroline)copper(II) [Cu(Valp)(2)phen] is showed for the first time. It crystallized in C2/c space group with unit cell dimensions of a = 14.939(1) A, b = 19.280(1) A, c = 9.726(1) A, beta = 97.27(2) degrees , V = 2778.8(4) A(3) and Z = 8. The carboxylates bond in an asymmetric chelating mode and the copper atom adopts a highly distorted octahedral coordination, characterized by the sum of the angles of 365.9 degrees around Cu(II) and its nearest atoms in the CuN(2)O(2) + O(2) chromophore instead of the expected 360 degrees for a basal square planar geometry found in most Cu(II) complexes. Molecules assemble three by three through slipped pi-pi stacking of the aromatic phen with respectively 3.519 and 3.527 A distances, in a head-to-tail arrangement. Studies of the anticonvulsant properties of this bioligand chelate evidenced its lack of efficacy in preventing MES-induced seizures. Interestingly, complex 4 protected mice against the Minimal Clonic seizures at doses that do not cause Rotorod toxicity, with an ED(50) documenting very potent anticonvulsant activity in this model of seizure, a particularly useful pharmacological profile of activity for the treatment of Petit Mal seizures.
Databáze: OpenAIRE
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