Synthesis, Structure of Nitrogen-Containing Phosphinogold(I) Ferrocenes. In vitro Activity against Bladder and Colon Carcinoma Cell Lines

The gold salt [(tht)AuCl] was reacted with [1-N,N-dimethylaminométhyl-2-diphenylphosphino]ferrocene (1) forming the bimetallic derivative 4. The reaction of methyl iodide and tetramethylammonium bromide on the chloride 4 produced the ammonium salt 5 and the bromide 6 respectively. New aminophosphines 2 and 3, which represent two of the rare phosphorylated metallocenes containing P(III)-N bond have also been coordinated to gold(I) to form 7 and 8. The presence of the ethoxy group in 7 provides evidence for the lability of one nitrogen-phosphorus bond. The X-ray structure of compounds 4 and 7 have been established. Both crystallize in space group P21/c, monoclinic, with a = 11.095(2) Å, b = 12.030(3) Å, c = 17.763(4) Å, β= 94.02(2)∘, Z = 4 for 4 and a = 14.863(3) Å, b = 8.036(5)Å, c = 18.062(5)Å, β =101.64(1)°, Z = 4 for 7. 197Au Mössbauer data are in good agreement with those for other linear P-Au-Cl containing complexes. The compounds were evaluated for in vitro anti-tumour activity against two human tumours. Differential cytotoxicity was observed with activity comparable to cisplatin, with the exception of one compound which was significantly more cytotoxic

Gentamicin-induced Nephrotoxicity - a Cell Biology Approach

Gentamicin is an antibiotic that exhibits a broad spectrum of activity and is particularly valuable in severe sepsis. Its use is, however, restricted because of the development of ototoxicity and nephrotoxicity (for the latter, see review in Ref. 1). At physiologic pH, the drug is highly charged and water soluble, and therefore it is practically unable to diffuse through biologic membranes.Nephrotoxicity has been related to a selective accumulation of gentamicin in the renal cortex [2, 3]. Morphologic lesions of proximal tubules have been documented in optic microscopy [4–6]. At the ultra-structural level, the earliest lesions observed concern the lysosomes, which show an accumulation of myeloid bodies [7–9].The mechanism of the gentamicin toxicity is, however, unknown. In this paper, we present studies on the localization of the drug at the cellular and subcellular levels, and on the enzymatic alterations that develop during gentamicin treatment