RESUMEN
BACKGROUND/AIM: Melanoma represents a big challenge for clinical treatment. Besides being the most aggressive and the deadliest form of skin cancer, it is often refractory to commonly used anticancer drugs. Hence, developing new anti-cancer agents is crucial to improve refractory melanoma treatment. Studies using palladium(II) complexes have reported antitumor effects on cancer cells. In this study, we aimed to determine the cytotoxic effect of three novel synthesized Pd(II) complexes with Schiff bases derived from 4-aminoacetophenone on the MDA-MB-435 melanoma cell line. MATERIALS AND METHODS: Cells were treated with ligand and Pd(II) complexes. Cell viability, morphology and death induction upon treatment were examined. RESULTS: Novel synthesized Pd(II) complexes led to decreased viability of cells. They also induced morphological alterations and cell death, mainly in the C3 complex. CONCLUSION: The novel synthesized complexes have a significant cytotoxic effect on cell line MDA-MB-435, especially C3 and can be considered as an antitumor agent for further studies.
Asunto(s)
Acetofenonas/química , Antineoplásicos/uso terapéutico , Melanoma/tratamiento farmacológico , Compuestos Organometálicos/uso terapéutico , Paladio/uso terapéutico , Bases de Schiff/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológico , Antineoplásicos/síntesis química , Muerte Celular , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Técnicas In Vitro , Ligandos , Compuestos Organometálicos/síntesis química , Paladio/química , Rodaminas , Bases de Schiff/químicaRESUMEN
Two novel triruthenium clusters, [Ru3(µ3-O)(µ-OOCCH3)6(NO)L2]PF6 (Lâ¯=â¯4acetylpyridine, 1, or 4tertbutylpyridine, 2) release NO. Their spectroscopic and electrochemical characterization confirmed their structure. These complexes efficiently deliver NO in solution under irradiation at λirradâ¯=â¯377â¯nm and/or through chemical reduction with ascorbic acid. Clusters 1 and 2 elicit vasodilation and, at concentrations of 10-5â¯M, can relax up to 100% of pre-contracted rat aorta. Complex 2 is more cytotoxic to murine melanoma B16F10 cells than complex 1: at 50 times lower concentration than complex 1, complex 2 decreases cell viability to 50% in the dark or under irradiation with visible light (λirradâ¯=â¯527â¯nm). The higher cytotoxicity of complex 2 can be assigned to its larger hydrophobicity, promoted by the methylated tertbutylpyridine ancillary ligand in its structure. Investigation into human serum albumin (HSA) fluorescence quenching by clusters 1 or 2 revealed that complex 2 quenches HSA luminescence with a very high Stern-Vomer constant (KSVâ¯=â¯9.49â¯×â¯107â¯M-1 at Tâ¯=â¯298â¯K) and suggested that the nature of the interaction between complex 2 and HSA is hydrophobic (ΔHâ¯=â¯80.81â¯kJ/mol and ΔSâ¯=â¯334.71â¯J/Kâ¯mol). HSA lifetime and circular dichroism data pointed to a static quenching mechanism for both complexes. Together, our results show that a hydrophobic substituent in the cluster ancillary ligand improves NO release ability, cytotoxicity, and interaction with a bio-target.
Asunto(s)
Aorta/fisiopatología , Complejos de Coordinación , Simulación del Acoplamiento Molecular , Óxido Nítrico , Rutenio , Vasodilatación/efectos de los fármacos , Animales , Línea Celular Tumoral , Complejos de Coordinación/síntesis química , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Citotoxinas/síntesis química , Citotoxinas/química , Citotoxinas/farmacología , Humanos , Ligandos , Masculino , Ratones , Óxido Nítrico/química , Óxido Nítrico/farmacología , Ratas , Ratas Wistar , Rutenio/química , Rutenio/farmacología , Vasodilatadores/síntesis química , Vasodilatadores/química , Vasodilatadores/farmacologíaRESUMEN
We describe the use of cadmium telluride quantum dots (CdTe QDs) as antennas for the photosensitization of nitric oxide release from a ruthenium nitrosyl complex with visible light excitation. The CdTe QDs were capped with mercaptopropionic acid to make them water-soluble, and the ruthenium nitrosyl complex was cis-[Ru(NO)(4-ampy)(bpy)2](3+) (Ru-NO; bpy is 2,2'-bipyridine, and 4-ampy is 4-aminopyridine). Solutions of these two components demonstrated concentration-dependent quenching of the QD photoluminescence (PL) as well as photoinduced release of NO from Ru-NO when irradiated by 530 nm light. A NO release enhancement of â¼8 times resulting from this association was observed under longer wavelength excitation in visible light range. The dynamics of the quenching determined by both PL and transient absorption measurements were probed by ultrafast flash photolysis. A charge transfer mechanism is proposed to explain the quenching of the QD excited states as well as the photosensitized release of NO from Ru-NO.