Toxicity quantitative structure--activity relationships of colchicines

J Med Chem. 1981 May;24(5):636-9. doi: 10.1021/jm00137a031.

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.

MeSH terms

  • Animals
  • Chemical Phenomena
  • Chemistry
  • Colchicine / analogs & derivatives*
  • Colchicine / toxicity
  • Lethal Dose 50
  • Mice
  • Structure-Activity Relationship

Substances

  • Colchicine