title: Platinum(II) and palladium(II) complexes with (N,N') and (C,N,N')- ligands derived from pyrazole as anticancer and antimalarial agents: synthesis, characterization and in vitro activities.
abstract: The study of the reactivity of three 1-(2-dimethylaminoethyl)-1H-pyrazole derivatives of general formula [1-(CH(2))(2)NMe(2)}-3,5-R(2)-pzol] {where pzol represents pyrazole and R=H (1a), Me (1b) or Ph (1c)} with [MCl(2)(DMSO)(2)] (M=Pt or Pd) under different experimental conditions allowed us to isolate and characterize cis-[M{κ(2)-N,N'-{[1-(CH(2))(2)NMe(2)}-3,5-R(2)-pzol])}Cl(2)] {MM=PtPt (2a-2c) or Pd (3a-3c)} and two cyclometallated complexes [M{κ(3)-C,N,N'-{[1-(CH(2))(2)NMe(2)}-3-(C(5)H(4))-5-Ph-pzol])}Cl] {M=Pt(II) (4c) or Pd(II) (5c)}. Compounds 4c and 5c arise from the orthometallation of the 3-phenyl ring of ligand 1c. Complex 2a has been further characterized by X-ray crystallography. Ligands and complexes were evaluated for their in vitro antimalarial against Plasmodium falciparum and cytotoxic activities against lung (A549) and breast (MDA MB231 and MCF7) cancer cellular lines. Complexes 2a-2c and 5c exhibited only moderate antimalarial activities against two P. falciparum strains (3D7 and W2). Interestingly, cytotoxicity assays revealed that the platinacycle 4c exhibits a higher toxicity than cisplatin in the three human cell lines and that the complex 2a presents a remarkable cytotoxicity and selectivity in lung (IC(50)=3 μM) versus breast cancer cell lines (IC(50)>20 μM). Thus, complexes 2c and 4c appear to be promising leads, creating a novel family of anticancer agents. Electrophoretic DNA migration studies in presence of the synthesized compounds have been performed, in order to get further insights into their mechanism of action.
authors: Laboratori de Química Orgànica, Facultat de Farmàcia, Institut de Biomedicina, (IBUB), Universitat de Barcelona, Barcelona, Spain.
authors: Josefina
authors: J
authors: Quirante
authors: Daniel
authors: D
authors: Ruiz
authors: Asensio
authors: A
authors: Gonzalez
authors: Concepción
authors: C
authors: López
authors: Marta
authors: M
authors: Cascante
authors: Roldán
authors: R
authors: Cortés
authors: Ramon
authors: R
authors: Messeguer
authors: Carme
authors: C
authors: Calvis
authors: Laura
authors: L
authors: Baldomà
authors: Aurélie
authors: A
authors: Pascual
authors: Yann
authors: Y
authors: Guérardel
authors: Bruno
authors: B
authors: Pradines
authors: Mercè
authors: M
authors: Font-Bardía
authors: Teresa
authors: T
authors: Calvet
authors: Christophe
authors: C
authors: Biot
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D053837:DNA Cleavage; D004278:DNA, Superhelical / Q000737:chemistry; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D008968:Molecular Conformation; D010165:Palladium; D010963:Plasmodium falciparum / Q000187:drug effects; D010984:Platinum; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000962:Antimalarials; D000970:Antineoplastic Agents; D056831:Coordination Complexes; D004278:DNA, Superhelical; D011720:Pyrazoles; D010984:Platinum; D010165:Palladium