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The dynamic and crucial role of tubulin in different cellular functions rendered it a promising target in anticancer drug development. Combretastatin A-4 (CA-4), an inhibitor of tubulin polymerization isolated from natural sources, is a lead molecule with significant cytotoxicity against tumour cells. Owing to its non polar nature it exhibits low solubility in natural biological fluids, thereby prompting the development of new CA-4 based derivatives. The modification of this lead molecule was mostly carried out by keeping the crucial -orientation of the double bond intact, along with a trimethoxyphenyl aromatic ring, by employing different approaches. The issue of solubility was also addressed by the development of water soluble prodrugs of CA-4. The present review highlights the investigations into the parallel development of both new CA-4 based derivatives and prodrugs in the past few years.

In the present paper, seven heavy metals (Pb, Cd, Ni, Cu, Zn, Cr and Fe) in canned salmon, sardine and tuna fish were determined by using atomic absorption spectroscopy. Cadmium and lead levels were determined by graphite tube AAS whereas Ni, Cu, Cr and Fe were determined by flame AAS. Analytical results were validated by spiking the samples with various concentrations of these metals for recovery. The metal contents, expressed in microg/g, wet weight, varied depending upon the specie studied. The levels of Pb ranged from 0.03-1.20 microg-g(-1) with an average of 0.313 microg-g(-1) for salmon; 0.03-0.51 microg-g(-1) with an average of 0.233 microg-g(-1) for tuna and 0.13-1.97 microg-g(-1) with an average of 0.835 microg-g(-1) for sardines. The levels of Cd ranged from 0.02-0.38 microg-g(-1) with an average of 0.161 microg-g(-1) for salmon; 0.07-0.64 microg-g(-1) with an average of 0.227 microg-g(-1) for tuna and 0.010-0.690 microg-g(-1) with an average of 0.183 microg-g(-1) for sardines. Comparative evaluation of these metals in three varieties of fish showed that average concentration of lead in sardines is about 4 times and Ni about 3 times higher as compared to tuna. Generally, the levels of these metals follow the order sardine > salmon > tuna. The data generated in the present study compared well with the similar studies carried out in different parts of the world. The results indicate that canned fish, in general and tuna in particular, have concentrations within permissible limits of WHO/FAO levels for these heavy metals. Therefore, their contribution to the total body burden of these metals can be considered as negligibly small.

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