Quantitative structure-activity relationship analysis of combretastatins: a class of novel antimitotic agents.

Combretastatins and their synthetic analogues, having structural features resembling that of colchicine, also have similar modes of action. In this report we have correlated the cytotoxicity of combretastatins against the murine leukemic cell line L1210 with physicochemical parameters such as the summation of the Hansch-Fujita pi constant, which was used as an index of lipophilicity of the substituent groups on ring A (sigma pi a) and ring B (sigma pi b), the vector summation of the group dipole moments of ring A (sigma mu a) and ring B (sigma mu b), the nature of the linker chain between ring A and ring B (Bt-L), indicator parameters (NOH)a and (NOH)b, which represent the number of hydroxyl groups on ring A and ring B, respectively, and the summation of pi values of the substituents on the linker (sigma pi L). Cytotoxicity correlated well with (sigma pi b), (NOH)a, (Bt-L), and (sigma mu b), and the dependency on (sigma pi b) was found to be parabolic.