Heteroleptic mononuclear compounds of ruthenium(ii): synthesis, structural analyses, in vitro antitumor activity and in vivo toxicity on zebrafish embryos.

The limitations of platinum complexes in cancer treatment have motivated the extensive investigation into other metal complexes such as ruthenium. We herein present the synthesis and characterization of a new family of ruthenium compounds 1a-5a with the general formula [Ru(bipy)2L][CF3SO3]2 (bipy = 2,2'-bipyridine; L = bidentate ligand: N,N; N,P; P,P; P,As) which have been characterized by elemental analysis, ES-MS, 1H and 31P-{1H} NMR, FTIR and conductivity measurements. The molecular structures of four Ru(ii) complexes were determined by single crystal X-ray diffraction. All compounds displayed moderate cytotoxic activity in vitro against human A2780 ovarian, MCF7 breast and HCT116 colorectal tumor cells. Compound 5a was the most cytotoxic compound against A2780 and MCF7 tumor cells with an IC50 of 4.75 ± 2.82 µM and 20.02 ± 1.46 µM, respectively. The compounds showed no cytotoxic effect on normal human primary fibroblasts but rather considerable selectivity for A2780, MCF7 and HCT116 tumor cells. All compounds induce apoptosis and autophagy in A2780 ovarian carcinoma cells and some nuclear DNA fragmentation. All compounds interact with CT-DNA with intrinsic binding constants in the order 1a > 4a > 2a > 3a > 5a. The observed hyperchromic effect may be due to the electrostatic interaction between positively charged cations and the negatively charged phosphate backbone at the periphery of the double helix-CT-DNA. Interestingly, compound 1a shows a concentration dependent DNA double strand cleavage. In addition in vivo toxicity has been evaluated on zebrafish embryos unveiling the differential toxicity between the compounds, with LC50 ranging from 8.67 mg L-1 for compound 1a to 170.30 mg L-1 for compound 2a.

[Renal carcinoma with intranuclear inclusions associated with colon carcinoma]. / Carcinoma renal con inclusiones intranucleares asociado a carcinoma de colon.

OBJECTIVE: To report a case of renal cell carcinoma associated with carcinoma of the colon. METHODS: A right renal mass was detected during US control evaluation of a patient that had undergone surgery for rectosigmoid carcinoma 4 months earlier. A previous abdominal CT scan revealed a renal mass with characteristics of malignancy. Fine-needle aspiration biopsy showed clear cell renal carcinoma. This case was considered as two different and synchronous primaries, and the patient was submitted to surgery. RESULTS: Intestinal adhesions secondary to radiotherapy were found intraoperatively, but there was no evidence of local intestinal recurrence, and therefore nephrectomy was performed. The histopathological study demonstrated clear cell renal carcinoma with intranuclear inclusions. CONCLUSIONS: Although the patient may have a previous history of carcinoma at another site, the finding of a renal mass excludes synchronous tumors and nephrectomy should be the treatment of choice. The finding of clear cells in the cytological study supports the interpretation that these lesions were different primaries. Renal carcinoma should be included among the neoplasms with intranuclear inclusions.