Mechanism of Colchicine-Mitosis 



409 



NH.C0CH3 



CH30 



CH30 



CH30 



0CH3 



(VIII) 



(IX) 



= 



0CH3 



methylcolchicinic iiictliyl cllier has been demonstrated to be one of 

 the most effective derivatives in arresting mitoses in the stomach 

 epithelium of mice."- ^-- -^^ 



Substitutions in ring C are the most important, for they yield 

 substances with a greater antimitotic activity than colchicine."^- '^^ 

 These are derivatives of colchicamide (X) . (This abbreviated spell- 

 ing is to be preferred to colchicine amide or colchiceinamide, which 

 are to be found in the literature.) Thirtv-fi\c derivatives of this type 

 have been studied by Lettre,''*' who found A -methyl-, N-ethyl-. and 

 A^-dimethyl-colchicamide to be most effective in tissue-culture work, 

 the activity decreasing when longer side-chains were added to the 

 amino-group (Table 17.3). 



Other derivatives with more extensive changes in ring C, for in- 

 stance with a six-carbon aromatic ring C, coJchinol series (XI) , or 



TABLE 17.2 

 Minimal Effective Antimitotic Dose of TMCA Derivatives on Corneal Mitoses 

 OF Mice, Six Hours After Injection, Expressed as the Fraction of the LD 50 In- 

 creasing the Mitotic Index Above That of Controls and Minimal Effective 

 Antimitotic Doses in Various Tissues of Mice 

 (After Goldberg et al .^^) 



