targeting of mitochondria-endoplasmic reticulum by fluorescent macrocyclic compounds针对荧光mitochondria-endoplasmic网的大环化合物.pdf

Targeting of Mitochondria-Endoplasmic Reticulum by Fluorescent Macrocyclic Compounds ˜ Carla Cruz*, Elisa Cairrao, Samuel Silvestre, Luiza Breitenfeld, Paulo Almeida, Joao A. Queiroz ˜ ˆ ´ ˜ CICS-UBI - Centro de Investigac¸ao em Ciencias da Saude, Universidade da Beira Interior, Covilha, Portugal Abstract Background: Useful probes of the intracellular environment that target a specific organelle in order to allow direct observation of the changes in these regions is of high current interest. Macrocyclic ligands have already revealed themselves as important selective hosts in some biological applications, forming stable and specific complexes. Therefore, in this paper, several macrocyclic ligands are evaluated as potential molecular probes. Methodology: Four polyammonium macrocycles and one macrotricyclic bearing pyridine and phenanthroline chromophores have been synthesised and evaluated as molecular probes. The cytotoxicity of the compounds has been analyzed using human breast cancer cells (MCF-7), non-cancerous human dermal fibroblasts (NHDF) and human adult dermal skin fibroblasts from a breast cancer patient (P14). All the compounds showed low toxicity at concentrations ranging from 10 nM to 10 mM, except for [32]phen N which proved to be highly cytotoxic for MCF-7 cells. Flow cytometry studies 2 4 evidenced that the percentage of apoptotic and necrotic MCF-7 and NHDF cells induced by the compounds is considerably low. Also, flow cytometry analysis showed that some compounds seem to mod