Toxicity quantitative structure--activity relationships of colchicines.
A method for extracting LD50 values from antitumor test data is described. A quantitative structure--activity relationship (QSAR) for 7- and 10-substituted colchicines is presented. This correlation equation closely parallels that which had been derived earlier for potency. This result indicates that attempts to modify 7- and 10-substituted colchicines in order to decrease toxicity will likely produce a simultaneous decrease in potency. Ring A modified colchicines do not obey the potency and toxicity correlations. 4-Substituted colchicines appear promising in terms of decreased toxicity, greater ILS, and a broader therapeutic range.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D003078:Colchicine / Q000031:analogs & derivatives* / Q000633:toxicity; D007928:Lethal Dose 50; D051379:Mice; D013329:Structure-Activity Relationship
D003078:Colchicine