Quantitative structure-activity relationships of colchicines against P388 leukemia in mice

Abstract

A quantitative structure-activity relationship (QSAR) was derived for colchicine and 14 analogs acting against [mouse] P388 lymphocytic leukemia in mice cells. Twelve additional compounds were synthesized to reinforce and confirm the correlation. There is a parabolic dependence of antitumor potency on the partition coefficient with log P0 = 1.17. When an amino N is present on the B ring, increased potency is favored by acylation of that N. The most potent compound of the series was the 7-fluoroacetamido analog. Strong electron-withdrawing groups substituted at the 10 position of the tropolone ring destroy activity. Electron-releasing groups at position 10 improve potency slightly but have a limited effect.