Relationship between electronic structure and cytotoxic activity of tropolones.

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 (muG, muESP-G, muW and muESP-W) and heats of formation (deltaHf) 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 deltadeltaHf, HOMO energy (EH) and muw. The cytotoxic activity of the five tropone derivatives [17-21] might depend on the QSAR parameters deltadeltaHf, LUMO energy (EL) and muESP-G. The results of the present study suggest the applicability of theoretical calculations such as frontier molecular orbital, dipole moments and deltadeltaHf in the prediction of the cytotoxic activity of tropolone derivatives.