Synthesis of Dipyridylaminoperylenediimide-Metal Complexes and Their Cytotoxicity Studies.

A new family of perylenediimide (PDI) silver and copper complexes has been successfully synthesized by reacting ortho- and bay-substituted (dipyrid-2',2″-ylamino)perylenediimide ligands with metal phosphine fragments. The coordination of the metal center did not reveal a significant effect on the photophysical properties, which are mainly due to the PDI ligands, and in some cases quenching of the luminescence was observed. The antiproliferative effect of the free perylenediimide ligands and the metalloPDI complexes against the cervix cancer cell line HeLa was determined by MTT assay. The free perylenediimide ligands exhibited a moderate cytotoxic activity, but the coordination of silver or copper to the dypyridylamino fragment greatly enhanced the activity, suggesting a synergistic effect between the two fragments. In attempts to elucidate the cellular biodistribution of the PDIs and the complexes, a colocalization experiment using specific dyes for the lysosomes or mitochondria as internal standards revealed a major internalization inside the cell for the metal complexes, as well as a partial mitochondrial localization.

Biological Activity of NHC-Gold-Alkynyl Complexes Derived from 3-Hydroxyflavones.

In this paper we describe the synthesis of new N-heterocyclic carbene (NHC) gold(I) derivatives with flavone-derived ligands with a propargyl ether group. The compounds were screened for their antimicrobial and anticancer activities, showing greater activity against bacteria than against colon cancer cells (Caco-2). Complexes [Au(L2b)(IMe)] (1b) and [Au(L2b)(IPr)] (2b) were found to be active against both Gram-positive and Gram-negative strains. The mechanism of action of 1b was evaluated by measurement of thioredoxin reductase (TrxR) and dihydrofolate reductase (DHFR) activity, besides scanning electron microscopy (SEM). Inhibition of the enzyme thioredoxin reductase is not observed in either Escherichia Coli or Caco-2 cells; however, DHFR activity is compromised after incubation of E. coli cells with complex 1b. Moreover, loss of structural integrity and change in bacterial shape is observed in the images obtained from scanning electron microscopy (SEM) after treatment E. coli cells with complex 1b.

Sulfonamide-Derived Dithiocarbamate Gold(I) Complexes Induce the Apoptosis of Colon Cancer Cells by the Activation of Caspase 3 and Redox Imbalance.

Two new families of dithiocarbamate gold(I) complexes derived from benzenesulfonamide with phosphine or carbene as ancillary ligands have been synthesized and characterized. In the screening of their in vitro activity on human colon carcinoma cells (Caco-2), we found that the more lipophilic complexes-those with the phosphine PPh3-exhibited the highest anticancer activity whilst also displaying significant cancer cell selectivity. [Au(S2CNHSO2C6H5)(PPh3)] (1) and [Au(S2CNHSO2-p-Me-C6H4)(IMePropargyl)] (8) produce cell death, probably by intrinsic apoptosis (mitochondrial membrane potential modification) and caspase 3 activation, causing cell cycle arrest in the G1 phase with p53 activation. Besides this, both complexes might act as multi-target anticancer drugs, as they inhibit the activity of the enzymes thioredoxin reductase (TrxR) and carbonic anhydrase (CA IX) with the alteration of the redox balance, and show a pro-oxidant effect.

Aftosis compleja idiopática. Diagnóstico diferencial / Idiophatic complex aphthosis. Differential diagnosis

Presentamos el caso de una paciente adolescente, estudiada desde los 11 años por episodios de úlceras genitales asociados a aftas bucales. Tras llevar a cabo un complejo proceso de diagnóstico diferencial, se descartó cualquier tipo de agente causal y se etiquetó el cuadro como una aftosis compleja idiopática, que se resolvió espontáneamente aplicando tratamiento sintomático. A pesar de haberse descartado por el momento una enfermedad de Behçet, la paciente es controlada periódicamente, dada la dificultad diagnóstica de esta entidad sobre todo durante los primeros años de evolución (AU)

We report the case of a teenage patient studied since she was 11 years old by episodes of genital ulcers associated with aphthous stomatitis. After carrying out a complex process of differential diagnosis, any kind of causal agent was ruled out and we got the diagnostic of complex aphthosis idiopathic, which resolved spontaneously applying symptomatic treatment. Although having ruled out Behcet’s disease, the patient is monitored periodically, given the difficulty in diagnosing this entity especially during the first years of evolution (AU)