404 



Colchicine 



chemical reactivity. After studying these simple spindle poisons, some 

 other substances acting like colchicine, or those with complex mole- 

 cular structure will be examined briefly. The properties of colchicine 

 will then be compared to those of other poisons. 



1J.4-1: Colchicine derivatives. These have been studied from 

 three main points of view: their toxicity, their antimitotic activity, 



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Colchicine 



-.7 -6 .5 _4 .3 .2 .1 _0 

 Solubility(log. mol. fraction) 



Fig. 17.2 — Relation between c-mitotic activity in the Allium test and solubility in water. 



Each dot or triangle corresponds to a different substance. The singular behavior of 



colchicine is evident. (After Ostergren, 1951 '") 



and their inhibition of tumor growth.-^ The spindle poisoning will 

 mainly interest us here, and it should be made clear that this is not 

 necessarily paralleled by other properties of these molecules. For in- 

 stance, it has long been known that colchiceine (II) is less toxic, and 

 also a weaker mitotic poison than colchicine. But desacetylcolchiceine, 

 trimethylcolcliicinic acid (III) ,'"'-^ does not interfere ai all with cell 

 division in animals, while it may, like colchicine, kill frogs by central 

 nervous paralysis. The opposite is also true; and results to be discussed 

 further point to the possibility of synthesizing derivatives with lower 

 toxicity and greater mitotic-poisoning effects than colchicine. 



