Toxicity and quantitative structure-activity relationships of colchicines

Journal of Medicinal Chemistry
1981.0

Abstract

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.

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