RESUMO
Two innovative early/late Ti-Pt-heterobimetallic complexes were synthesized, characterized, and screened in cell-based assays using several human (SW480 and MDA-MB-231) and murine cancer cell lines (CT26 and EMT6) as well as a non-cancerous cell line (HMEC). The combination of the two metals - titanium(IV) and platinum (IV) - in a single molecule led to a synergistic biological activity (higher anti-proliferative properties than a mixture of each of the corresponding monometallic complexes). This study also investigated the benefits of associating a metal-free terpyridine moiety (with intrinsic biological activity) with a water-soluble titanocene fragment. The present work reveals that these combinations results in water-soluble titanocene compounds displaying an anti-proliferative activity down to the submicromolar level. One of these complexes induced an antitumor effect inâ vivo in CT26 tumor bearing BALB/C mice. The terpyridine moiety was also used to track the complex inâ vitro by multiphoton microscopy imaging.
Assuntos
Antineoplásicos , Proliferação de Células , Camundongos Endogâmicos BALB C , Platina , Solubilidade , Titânio , Água , Animais , Humanos , Titânio/química , Titânio/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Proliferação de Células/efeitos dos fármacos , Camundongos , Platina/química , Platina/farmacologia , Água/química , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/síntese química , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Compostos Organometálicos/síntese química , Desenho de Fármacos , Cátions/química , Cátions/farmacologia , Estrutura MolecularRESUMO
A phosphine gold(I) and phosphine-phosphonium gold(I) complexes bearing a fluorescent coumarin moiety were synthesized and characterized. Both complexes displayed interesting photophysical properties: good molar absorption coefficient, good quantum yield of fluorescence, and ability to be tracked inâ vitro thanks to two-photon imaging. Their inâ vitro and inâ vivo biological properties were evaluated onto cancer cell lines both human and murine and into CT26 tumor-bearing BALB/c mice. They displayed moderate to strong antiproliferative properties and the phosphine-phosphonium gold(I) complex induced significant inâ vivo anti-cancer effect.
Assuntos
Antineoplásicos , Neoplasias , Fosfinas , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Ouro/farmacologia , Camundongos , Fosfinas/farmacologiaRESUMO
Three new gold(I)-coumarin-based trackable therapeutic complexes and two non-trackable analogues have been synthesised and fully characterised. They all display anti-proliferative properties on several types of cancer cell lines, including those of colon, breast, and prostate. Two complexes displayed significant anti-inflammatory effects; one displayed pro-inflammatory behaviour; this highlights the impact of the position of the fluorophore on the caffeine scaffold. Additionally, the three coumarin derivatives could be visualised in vitro by two-photon microscopy.
Assuntos
Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Cafeína/análogos & derivados , Cafeína/farmacologia , Complexos de Coordenação/farmacologia , Cumarínicos/farmacologia , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Anti-Inflamatórios/efeitos da radiação , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/efeitos da radiação , Cafeína/síntese química , Cafeína/efeitos da radiação , Linhagem Celular Tumoral , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Complexos de Coordenação/efeitos da radiação , Cumarínicos/síntese química , Cumarínicos/química , Cumarínicos/efeitos da radiação , Fluorescência , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Corantes Fluorescentes/farmacologia , Corantes Fluorescentes/efeitos da radiação , Ouro/química , Células HEK293 , Humanos , Microscopia de Fluorescência por Excitação Multifotônica/métodos , Raios UltravioletaRESUMO
Two new gold(i)-BODIPY-imidazole based trackable therapeutic bimetallic complexes have been synthesized and fully characterized. They display strong antiproliferative properties on several types of cancers including colon, breast, and prostate and one of them presents a significant anti-inflammatory effect. Additionally, the two compounds could be visualised in vitro by confocal microscopy in the submicromolar range.
Assuntos
Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Compostos de Boro/química , Complexos de Coordenação/farmacologia , Ouro/química , Imidazóis/química , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Descoberta de Drogas , Corantes Fluorescentes/química , HumanosRESUMO
A novel Ti/111In-heterometallic radiotheranostic along with non-radioactive Ti/In, Ti/Lu, and Ti/Y analogues has been reported, thanks to the design of a challenging synthesis of the first titanocene-DOTA ligand. The corresponding titanocene-BODIPY complex was developed for in vitro tracking by optical imaging. The different complexes were characterized and their antiproliferative properties were evaluated on three cancer cell lines (A2780, B16F1, and PC3). As a proof of concept, initial studies in healthy mice were performed with a Ti/111In derivative to obtain information about its uptake, its biodistribution, and its excretion. Confocal microscopy experiments were performed with fluorescent complexes to track it in vitro.