RESUMEN
The synthesis with full structural characterization including elemental analysis and 1H, 13C, 11B and 19F NMR, FT-IR and MALDI-TOF spectral data, along with the florescence sensing behavior of a new resorcin[4]arene cavitand 3 bearing multiple BODIPY sites achieved by the Cu-catalyzed azide-alkyne cycloaddition (CuAAC) is being reported. The spatial orientation of multiple BODIPY-1,2,3-triazole arms based on the macrocyclic rigid core is of great interest since the resulting structure has been utilized as a fluorescent chemosensor for numerous metal cations. In particular, a remarkable decrease in the fluorescence emission towards Cu(ii) ions, i.e., "turn-off" response, has been obtained giving rise to an optical sensor for the detection of triazole fungicides, namely tebuconazole, triadimenol, triadimefon, i.e. "turn-on" response. Such a molecular system, hence, can be feasibly applied as a dual optical sensor, i.e. "a turn-on-off-on" system, for dangerous contaminants such as heavy metals and pesticides.
RESUMEN
High photodynamic activity was observed for hexadeca-cationic zinc, magnesium, and metal-free phthalocyanines (Pcs) and tetrapyrazinoporphyrazines with EC50 values as low as 5 nM (MCF-7 cells) for the best compound; this activity was several times better than that of clinically established photosensitizers verteporfin, temoporfin, S3AlOHPc, or protoporphyrin IX. This lead compound was characterized by low dark toxicity (TC50 = 369 µM), high efficiency against other cell lines (HCT 116 and HeLa), and possible activation by light above 680 nm. The excellent photodynamic activity resulted from the rigid spatial arrangement of the quaternized triazole moieties above and below the Pc core, as confirmed by X-ray crystallography. The triazole moieties thus formed two "cationic donuts" that protected the hydrophobic core against aggregation in water. The lysosomes were found to be the site of subcellular localization and were consequently the primary targets of photodynamic injury, resulting in predominantly necrotic cell death.
Asunto(s)
Indoles/química , Fármacos Fotosensibilizantes/química , Porfirinas/química , Pirazoles/química , Triazoles/química , Línea Celular Tumoral , Cristalografía por Rayos X , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Indoles/síntesis química , Indoles/farmacología , Isoindoles , Lisosomas/metabolismo , Conformación Molecular , Necrosis , Fotoquimioterapia , Fármacos Fotosensibilizantes/síntesis química , Fármacos Fotosensibilizantes/farmacología , Porfirinas/síntesis química , Porfirinas/farmacología , Pirazoles/síntesis química , Pirazoles/farmacología , Relación Estructura-Actividad , Triazoles/síntesis química , Triazoles/farmacologíaRESUMEN
Newly synthesized zinc phthalocyanine bearing sixteen quaternized imidazolyl moieties on the periphery displays high water-solubility, lack of aggregation and high singlet oxygen quantum yield in water (ΦΔ > 0.33). The in vitro tests indicated excellent anticancer photodynamic activity (EC50 = 36.7 nM) and low dark toxicity to non-cancerous cells (TC50 = 395 µM).