/Mechanism of Colchicine-Mitosis 



407 



that c-tumors (root-tip swellings) occtir with solutions which arc de- 

 void of any mitotic action. The hypothesis has been put forward that 

 colchicoside may be some kind of detoxication product of colchicine, 

 a fact which may help to explain die resistance of Colchiciun towards 

 colchicine (cf. Subsection 17.2-2) . 



The principal changes affecting the action of colchicine are those 

 affecting the .V-substituted radicals in ring B and the esters of ring 



NH.COCH3 



CH30 



= 



0CH3 



NH.COCH3 



OCH3 



(VII) Colchicine 

 Isocolchicine 



C. Before considering some of these derivatives, it is important to 

 stud\ the residts obtained with an isomer of colchicine, isocolchicine, 

 (VII) in which the positions of the O and O-CHo radicals of ring C 

 are reversed. i^*'- ^'^'- *'•"' 



The activity of /.socolchicine has been studied on Allium root 

 tips^^' and on fibroblast cultures.*"'^ Solubility and thermodynamic 

 acti\ity differ considerably from those of colchicine, ^\'hilc the latter 

 is soluble in approximately all proportions in water, /5ocolchicine 

 has a solubility of oO.OOOx iO'M// 1. The activity thresholds stand at 

 150 for colchicine and 14,000 X 10''iU/l for the /io-compoiuid, the 

 thermodynamic activity of which is 0.28, that is to say, about a thous- 

 and times higher than that of colchicine. As a conclusion of this 

 work, it appears "that colchicine, with its low thermodynamic activity 

 is a typical representative of the chemically acting substances, while 

 /.^ocolchicine with its 900 times higher thermodynamic activity be- 

 longs to the type of unspecifically acting substances." ^i' /iocolchicine 

 interferes thus w'nh mitosis like the many substances mentioned in 

 the previous paragraph of this chajitcr. In fibroblast cid tines, the 

 difference is not quite so great, for ?5ocolchicine is only 50 times less 

 active than colchicine. Two other similar molecides, ethyl-colchi- 

 ceine and isoethylcolcliiceine, were compared on the same material: 

 the second was about 200 times less active than the first. These sub- 

 stances have been isolated from C.olrliicinn. Other iso- derivatives of 



