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 (B(t-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, (B(t-L), and (SIGMA-mu-b), and the dependency on (SIGMA-pi-b) was found to be parabolic.