Tubulin interfering with

Colchicine has a long history of successful use and was the treatment of choice for many years. It is used infrequently today because of its low therapeutic index. Colchicine is thought to exert its anti-inflammatory effects by interfering with the function of mitotic spindles in neutrophils by binding of tubulin dimers this inhibits phagocytic activity. 

Maytansine and related compounds inhibit cell division in sea urchin eggs at concentrations of 0.04 j/g/ml (6 x 10-8 M), possibly by interfering with the polymerization of tubulin. This effect bears some resemblance to the action of the vinca alkaloids such as vincristine. Maytansine inhibits the growth of KB cells at levels of 10 5 fig/ml. 

Although the compounds were isolated in quantities of only a few milligrams per kilogram of crude plant leaves, extensive work on a variety of animal tumor systems led to eventual clinical use of these bases, first alone and later in conjunction with other materials, in the treatment of Hodgkin s disease and acute lymphoblastic leukemia. Their main effect appears to be binding tightly to tubulin, the basic component of microtubules found in eukaryotic cells, thus interfering with its polymerization and hence the formation of microtubules required for tumor proliferation (82). 

Thiabendazole inhibits the helminlh-speciflc enzyme fu-maralc reductase. It is not known whether metal ions are involved or if the inhibition of the enzyme is related to thiabendazole s anthclmintie effeel. Benzimidazole anthelmin-tie drugs such as thiabendazole and mebendazole also aire.st nematode cell division in metaphase by interfering with microtubule assembly."- They exhibit a high affinity for tubulin, (he precursor protein for tnicrotiibulc synthesis. 

Other binding sites have been postulated according to tubulin interfering agents with a binding behaviour distinct to that of taxanes, vinca alkaloids and colchinoids. 

Extraction can remove not only the solnble tubnlin from the cell, bnt also the polymerized microtnbules. Extraction shonld be done carefully, and extraction time shonld be optimized to remove soluble tubulin from the cells while not interfering with the microtubnle network. 

---