Relationship between Electronic Structure and Cytotoxic Activity of Tropolones

Abstract

A structure-activity relationship of the cytotoxic activity of tropolone derivatives was discussed, using theoretical calculations. In order to clearly divide the tropolones into two structurally analogous groups, four different dipole moments (μ_G, μ_ESP-G, μ_W and μ_ESP-W) and heats of formation (ΔH_f) of the tropolones [1-21] were calculated in the gas-phase and in water-solution by the conductor-like screening model/parametric method 3 (COSMO/PM3). The cytotoxic activities of the tropolones and 2-methoxytropones seem to be related to the three QSAR parameters ΔΔH_f, HOMO energy (E_H) and μ_w. The cytotoxic activity of the five tropone derivatives [17-21] might depend on the QSAR parameters ΔΔH_f, LUMO energy (E_L) and μ_ESP-G. The results of the present study suggest the applicability of theoretical calculations such as frontier molecular orbital, dipole moments and ΔΔH_f in the prediction of the cytotoxic activity of tropolone derivatives.