title: On the cytotoxic activity of Pd(II) complexes of N,N-disubstituted-N'-acyl thioureas.
abstract: The rational design of anticancer drugs is one of the most promising strategies for increasing their cytotoxicity and for minimizing their toxicity. Manipulation of the structure of ligands or of complexes represents a strategy for which is possible to modify the potential mechanism of their action against the cancer cells. Here we present the cytotoxicity of some new palladium complexes and our intention is to show the importance of non-coordinated atoms of the ligands in the cytotoxicity of the complexes. New complexes of palladium (II), with general formulae [Pd(PPh3)2(L)]PF6 or [PdCl(PPh3)(L)], where L=N,N-disubstituted-N'-acyl thioureas, were synthesized and characterized by elemental analysis, molar conductivity, melting points, IR, NMR((1)H, (13)C and (31)P{(1)H}) spectroscopy. The spectroscopic data are consistent with the complexes containing an O, S chelated ligand. The structures of complexes with N,N-dimethyl-N'-benzoylthiourea, N,N-diphenyl-N'-benzoylthiourea, N,N-diethyl-N'-furoylthiourea, and N,N-diphenyl-N'-furoylthiourea were determined by X-ray crystallography, confirming the coordination of the ligands with the metal through sulfur and oxygen atoms, forming distorted square-planar structures. The N,N-disubstituted-N'-acyl thioureas and their complexes were screened with respect to their antitumor cytotoxicity against DU-145 (human prostate cancer cells), MDA-MB-231 (human breast cancer cells) and their toxicity against the L929 cell line (health cell line from mouse).
authors.affiliation: Laboratorio de Síntesis Orgánica, Facultad de Química, Universidad de La Habana, La Habana, Cuba. Electronic address: anap@fq.uh.cu.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Plutín
authors.affiliation: Laboratorio de Síntesis Orgánica, Facultad de Química, Universidad de La Habana, La Habana, Cuba.
authors.forename: Raúl
authors.initials: R
authors.lastname: Mocelo
authors.affiliation: Laboratorio de Síntesis Orgánica, Facultad de Química, Universidad de La Habana, La Habana, Cuba.
authors.forename: Anislay
authors.initials: A
authors.lastname: Alvarez
authors.affiliation: Laboratorio de Síntesis Orgánica, Facultad de Química, Universidad de La Habana, La Habana, Cuba.
authors.forename: Raúl
authors.initials: R
authors.lastname: Ramos
authors.affiliation: Instituto de Química de São Carlos, Universidade de São Paulo, São Carlos, SP, Brazil.
authors.forename: Eduardo E
authors.initials: EE
authors.lastname: Castellano
authors.affiliation: Departamento de Gerontologia, Universidade Federal de São Carlos, São Carlos, SP, Brazil.
authors.forename: Marcia R
authors.initials: MR
authors.lastname: Cominetti
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos, São Carlos, SP, Brazil.
authors.forename: Angelica E
authors.initials: AE
authors.lastname: Graminha
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos, São Carlos, SP, Brazil.
authors.forename: Antonio G
authors.initials: AG
authors.lastname: Ferreira
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos, São Carlos, SP, Brazil. Electronic address: daab@ufscar.br.
authors.forename: Alzir A
authors.initials: AA
authors.lastname: Batista
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D003603:Cytotoxins / Q000138:chemical synthesis / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D010165:Palladium / Q000737:chemistry*; D013890:Thiourea / Q000031:analogs & derivatives*
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D003603:Cytotoxins; D010165:Palladium; D013890:Thiourea
keywords: Acyl thiourea derivatives; Cytotoxicity; Pd (II) complexes; Triphenylphosphine; X-ray structures