RESUMEN
Mitochondrial damage will hinder the energy production of cells and produce excessive ROS (reactive oxygen species), resulting in cell death through autophagy or apoptosis. In this paper, four cyclometalated iridium(III) complexes (Ir1: [Ir(piq)2L]PF6; Ir2: [Ir(bzq)2L]PF6; Ir3: [Ir(dfppy)2L]PF6; Ir4: [Ir(thpy)2L]PF6; piq = 1-phenylisoquinoline; bzq = benzo[h]quinoline; dfppy = 2-(2,4-difluorophenyl)pyridine;thpy = 2-(2-thienyl)pyridine; L = 1,10-phenanthroline-5-amine) were synthesized and characterized. Cytotoxicity tests show that these complexes have excellent cytotoxicity to cancer cells, and mechanism studies indicatethat these complexes can specifically target mitochondria. Complexes Ir1 and Ir2 can damage the function of mitochondria, subsequently increasing intracellular levels of ROS, decreasing MMP (mitochondrial membrane potential), and interfering with ATP energy production, which leads to autophagy and apoptosis. Furthermore, autophagy induced by Ir1 and Ir2 can promote cell death in coordination with apoptosis. Surprisingly, these four complexes also showed moderate antibacterial activity to S. aureusand P. aeruginosa.
Asunto(s)
Antibacterianos/farmacología , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Complejos de Coordinación/farmacología , Iridio/química , Mitocondrias/metabolismo , Células A549 , Antibacterianos/química , Antineoplásicos/química , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Complejos de Coordinación/química , Humanos , Espectroscopía de Resonancia Magnética/métodos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Quinolinas/química , Especies Reactivas de Oxígeno/metabolismo , Espectrometría de Masa por Ionización de Electrospray/métodos , Staphylococcus aureus/efectos de los fármacosRESUMEN
As the "powerhouse" of a cell, mitochondria maintain energy homeostasis, synthesize ATP via oxidative phosphorylation, generate ROS signaling molecules, and modulate cell apoptosis. Herein, three Re(I) complexes bearing guanidinium derivatives have been synthesized and characterized. All of these complexes exhibit moderate anticancer activity in HepG2, HeLa, MCF-7, and A549 cancer cells. Mechanism studies indicate that complex 3, [Re(CO)3(L)(Im)](PF6)2, can selectively localize in the mitochondria and induce cancer cell death through mitochondria-associated pathways. In addition, complex 3 can effectively depress the ability of cell migration, cell invasion, and colony formation.
Asunto(s)
Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Guanidina/química , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Renio/química , Antineoplásicos/química , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Humanos , Ligandos , Invasividad Neoplásica , Relación Estructura-ActividadRESUMEN
Quantitative evaluation on the vegetation recovery after the earthquake is of great scienti-fic significance for local ecological system rebuilding and regional social-economic sustainable deve-lopment. By taking the Longxi River Basin in Dujiangyan of Sichuan Province as an example, and employing the MODIS-NDVI time-series data, this paper illustrated the dynamic changes of the ve-getation cover rates in Longxi River basin before and after the 5.12 Wenchuan Earthquake by using Landsat data, and then time-space characters of the recovery rates of the damaged vegetation was quantified structurally by referring the factors of river-system and terrain. The results showed that the recovery of impaired vegetation coverage worked well from a holistic point of view, but the response of vegetation coverage to earthquake disaster showed a lagging-phenomenon. The recovery rate of damaged vegetation was significantly correlated to its distance to surrounding river systems, elevation, slope degree, and slope aspect. This finding could provide technical supports for decision-makers to intervene the recovering process after earthquake.