Mechanism of Colchicine-Mitosis 



405 



In [he AJIimii test, I) I mctli\l((>!(lii( ii)ic ociil (III) has been sh()\vn 

 to induce c-niitosis, but it is thought that the incchanisiii is (|uite dif- 

 Icrent from that of colchicine, and rchitcd to the amino grotij) of ring 

 B.i^' 1 his derivati\c has a marked toxicity, while even 20 j^er cent 

 solutions of colchicine are only slightly toxic for these plant cells. 



Before considering in some detail artificial colchicine derivatives, it 

 is important to remember that other closely related alkaloids exist in 



CHsO 



CH30 



COCH;j 



CH30 



CH30 



NHo 



CH3O 



O 



CH3O 



= 



OH 



OH 



(II) Colchiceine 



(III) Trimethylco!chicinic Acid 



Coh liicuNi, and also that colchicine is probably present in chemical 

 combination with a glucoside. DesmethyJcohhicine has been found 

 in preparations of colchicine;^^ it differs from colchicine only by one 

 methyl group missing in ring A. It has been proved that it jjoisons 

 mitosis like colchicine, and demonstrates that two methyl groups are 

 sufficient for this. It is probable that at least one is indispensable. 

 Work by Lettre is interesting in this connection.'"'' This author, 

 searching for mitotic poisons with a simpler chemical structure, and 

 basing his researches at the time on the old formula of \V^indaus in 

 ^vhich rings B and C are 6-membcred, showed that on fibroblasts in 

 tissue culture, niescaJine (IV) was without action, while a-phcnyl-^- 

 {^,4, ytrimethoxypliefiyl) -etJiylatnine (V) is active. Further simplifi- 

 cation demonstrated that spindle poisoning was retained in a-i)henyl- 

 (5 (p-metholxyphenyl) -ethylaminc (VI) , which was the simplest ))os- 

 sible poison of this group. 



Ihe exact chemical structure of several other substances from 

 Colchuum and closely related to colchicine is not known yet; they 

 probably differ from the parent molecule by relatively minor changes, 

 '""■ ""•''•■'' and are all more or less active against mitosis. 



In Colchicutn, a substance named colchicoside, resulting from a 

 glucosidic linkage of colchicine, the exact chemical nature of which 

 has not yet been established, has been isolated.''- It is of interest to 

 note ihat this poisons spindles, but is 40 times less active than colchi- 

 cine towards plant mitoses. With diluted solutions, it is observed 



