RESUMO
Herein, we present a comprehensive review focusing on synthetic strategies, detailed structural analysis, and anticancer activity investigations of complexes following the general formula [LnM(µ-diphosphine)M'Lm] where M = group 8 metal; M' = any transition metal; µ-diphosphine = bridging ligand; Ln and Lm = ligand spheres). Both homo- and heteromultimetallic complexes will be discussed in detail. We review in vitro, in vivo and in silico anticancer activity investigations, in an attempt to draw comparisons between the various complexes and derive structure-activity relationships (SAR). This review solely focuses on complexes falling under the general formula stated above that have been studied for their anticancer activities, other complexes falling into that scheme but which have not undergone anticancer testing are not included in this review. We compare the anticancer activities of these complexes to their mononuclear counterparts, and a positive control (cisplatin) when possible and present a summary of all existing data to date and attempt to draw some conclusions on the future development of these complexes.
Assuntos
Antineoplásicos , Complexos de Coordenação , Fosfinas , Elementos de Transição , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Humanos , Ligantes , Fosfinas/química , Fosfinas/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/síntese química , Elementos de Transição/química , Elementos de Transição/farmacologia , Relação Estrutura-Atividade , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura Molecular , Animais , Proliferação de Células/efeitos dos fármacosRESUMO
Herein, we describe the synthesis, full spectroscopic characterization, DFT (density functional theory) calculations, and single-crystal X-ray diffraction analyses of a series of osmium arene σ-germyl, germanate, σ-stannyl, and stannate complexes, along with their cytotoxic (anticancer) investigations. The known dimer complexes [OsCl2(η6-C6H6)]2 (1) and [OsCl2(η6-p-cymene)]2 (2) were reacted with PPh3 to form the known mononuclear complex [OsCl2(η6-p-cymene)(PPh3)] (3) and the new complex [OsCl2(η6-C6H6)(PPh3)] (6); complex 3 was reacted with GeCl2·(dioxane) and SnCl2 to afford, by insertion into the Os-Cl bond, the neutral σ-germyl and stannyl complexes [OsCl(η6-p-cymene)(PPh3)(GeCl3)] (7) and [OsCl(η6-p-cymene)(PPh3)(SnCl3)] (11), respectively, as a mixture of enantiomers. Similarly, the reaction of complex 6 with GeCl2·(dioxane) afforded [OsCl(η6-C6H6)(PPh3)(GeCl3)] (9). Complex 2, upon reaction with 1,1-bis(diphenylphosphino)methane (dppm), formed a mixture of [OsCl2(η6-p-cymene)(κ1-dppm)] (4) and [Os(η6-p-cymene)(κ2-dppm)Cl]+Cl- (5) when prepared in acetonitrile and a mixture of 4 and the dinuclear complex [[OsCl2(η6-p-cymene)]2(µ-dppm)] (0) when prepared in dichloromethane. By utilizing either isolated 4 or a mixture of 4 and 5, the synthesis of κ2-dppm germanate and stannate salts, [OsCl(η6-p-cymene)(κ2-dppm)]+GeCl3 - (8) and [OsCl(η6-p-cymene)(κ2-dppm)]+SnCl3 - (10), were accomplished via halide-abstracting reactions with GeCl2·(dioxane) or SnCl2, respectively. All resulting complexes were characterized by means of multinuclear NMR, FT-IR, ESI-MS, and UV/Vis spectroscopy. X-ray diffraction analyses of 4, 8, 9, 10, and 11 were performed and are reported. DFT studies (B3LYP, basis set LANL2DZ for Os, and def2-TZVPP for Sn, Ge, Cl, P, C, and H) were performed on complex 9 and the benzene analogue of complex 11, 11-benzene, to evaluate the structural changes and the effects on the frontier molecular orbitals arising from the substitution of Ge for Sn. Finally, complexes 3 and 7-11 were investigated for potential anticancer activities considering cell cytotoxicity and apoptosis assays against Dalton's lymphoma (DL) and Ehrlich ascites carcinoma (EAC) malignant cancer cell lines. The complexes were also tested against healthy peripheral blood mononuclear cells (PBMCs). All cell lines were also treated with the reference drug cisplatin to draw a comparison with the results obtained from the reported complexes. The study was further corroborated with in silico molecular interaction simulations and a pharmacokinetic study.