Organotin anticancer activity

Such studies allow a better imderstanding of the possible mechanisms involved in organotin anticancer activity but also show that such mechanisms may vary with the particular cell lines as well as with the nature of the specific organotin compound. The second finding indicates that particular organotin compounds should be studied on a variety of cell lines before being cast aside as being inactive. 

This survey of the literature data on the interactions of organotin(IV) cations with biologically active ligands demonstrates that this is still a very open field. Above all, it is necessary to emphasize that usage of such complexes to treat humans is not permitted at present. Consequently, all compounds examined and discussed here (although with promising anticancer activity) are in the exploratory research stage. 

There have been various reports of the anticancer activities of organotin species, eg. towards P388 lymphocytic leukemia in mice. Research work continues strongly in this area, but it appears that chemical use of organotin anticancer drugs is at the very best several years away. 

We have been involved in the synthesis and characterization of organotin polymers for over 30 years. The synthesis of organotin polymers was recently reviewed [2]. Much of our interest in organotin polymers is related to their antibacterial, anticancer, and antiviral activity [2-32], The antibacterial and anticancer activity of these polymers has been recently reviewed [2,3]. 

IV ANTICANCER ACTIVITY OF ORGANOTIN POLYMERS V. FUTURE WORK VI. REFERENCES... 

Here we briefly review some of the evaluations of organotin compounds with respect to their ability to inhibit cancer. Most of these studies involve simple cell culture studies, but they may be instructive as to what constitutes important structural considerations. The anticancer activity of small organotin compounds is well established. Here we will look at some specific examples to lay the foundation for our efforts. 

In the evaluation of a number of studies, Saxena and Huber found that the most active organotin species were the dialkyltin compounds. Brown found that triphenyltin acetate exhibited antitumor activity in mice, while triphenyltin chloride was inactive. She believed that the degree of water solubility was an important factor in the anticancer activity of the organotin compounds. 

In 1980 Crowe et al " published the first report on the anticancer activity of a series of diorganotin dihalides and complexed products of the general formula R2SnX22L, where 2L (bidentate) = phenanthroUne, bipyridyl, 2-aminomethylpyri-dine L (monodentate) = dimethylsrrlfoxide, pyridine X = halides and R = methyl, ethyl, propyl, butyl, or phenyl. They postulated that a somewhat stable organotin complex is needed for good activity. The diethyltin dichloride compounds were found to be the most active. 

A large variety of organotin carboxylates have been prepared, and their structures determined by X-ray diffraction. Part of the impetus for this work has been the search for anticancer drugs, and the aim of relating activity to structure. The early work on structure has been thoroughly reviewed,346 as well as recent developments,347 including the structural work on the organotin derivatives of amino acids and peptides.348... 

Most of these products have been incorporated into paper, plastics, textiles, and the like with only some loss in biological activity. [89] We will now move to the use of organotin polyamines as potent anticancer drugs. [74,74,96-100] Recently we synthesized a wide variety of organotin polymers derived from 4,6-diaminopyrimidines (Figure 3).[101]... 

The use of organotin-containing compounds as potential drugs in the war against cancer has occurred since the early 1970s with some but only mild suc-cess. We more recently began to focus on the anti-cancer activity of organotin polymers that we had made for other purposes and as part of our platinum anticancer effort. Here, we will briefly review these efforts. 

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