Cell lines organotin cytotoxicity

Inhibition of macromolecular synthesis, mitochondrial energy metabolism, and reduction of DNA synthesis, as well as direct interaction with the cell membrane (increase in cytosolic Ca2+ concentration), have been implicated in organotin-induced cytotoxicity [169, 170]. Promotion of oxidative and DNA damage in vivo has been detected [171]. Oxidative damage and increased concentration of intracellular calcium ions seem to be the major factors contributing to triorga-notin-induced apoptosis in many cell lines [172]. 

The toxicity for a series of di- and triorganotins was also found to correlate well with the hydrophobic characteristics (log P or Hansch jt) of the compounds against two mammalian cell lines (BALB/c mouse fibroblast 3T3 and mouse neuroblastoma Naa cells). The sequence of the cytotoxicity for the organotins was similar to those observed in earlier studies. " Another study by Babich and Borenfreund using bluegill sunfish BF-2 cell fines showed that there was a direct linear correlation between the cytotoxicity of a series of diorganotins and the lipophilicity of the compounds, with a correlation coefficient of 0.958. 

In searching for new structural variables for tin anti-tumor compounds, Gielen has proposed a number of perfluoroalkanecarboxylates, three of them being very active against seven tumor cell lines. His recent review on organotin compounds is an effort to systematize all kinetic and stereochemical evidence on most of their compounds with respect to results derived from cytotoxicity assays. ... 

Flufenamic acid (fluff) and organotin addncts have been evaluated for anti-proliferative activity. Among the compounds tested, [ -Bn2(fln)SnOSn(flu)-n-Bu2] and [n-Bu2Sn(flu)2] exhibited high cytotoxic activity against the cancer cell line A549.49... 

Very recently a family of diphenyltin(IV) compounds was tested in vitro against human tumor cell lines to assess their cytotoxic activity, and the same family of compounds was also tested for antioxidant efficiency in rat brain homogenate, showing that there is a structure-activity relationship in the latter case. The correlation suggests that selected molecular variables are prototype tracers for the calculation of inhibitory concentrations. Moreover there seems to be an inverse structure-response behavior among activities, since the most hydrophobic organotin molecule is the least active compound for cytotoxic assays, while it is the best in anti-oxidant tests. 

In vitro and in vivo studies have indicated that different organotin compounds show different cytotoxic effects on different types of cell lines. Thus, tributyltin and triphenyltin showed immunosuppressive behavior while trimethyltin and triethyltin compormds were nemotoxic. It is known that different organotin compounds show different effects on Na /K -ATPase activity. Fruther, different organotin halides have shown different effects on voltage-gated potassium currents in lymphocytes and nemoblastoma ceUs. ... 

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