Estimation of relationship between structure of newly synthesized dihydroimidazoles determined by a semiempirical molecular-orbital method and their cytotoxicity.

A semiempirical molecular-orbital method (CAChe 4.9, PM5) was applied to delineate the relationship between the cytotoxicity (evaluated by 50% cytotoxic concentration, CC(50)) of twelve dihydroimidazole derivatives, their molecular weight and the eleven chemical parameters (descriptors) determined by CONFLEX/PM5 method. There was no correlation between the CC(50) value and heat of formation, dipole moment, E(HOMO), E(LUMO), absolute hardness (eta), absolute electron negativity (chi), reaction index (omega), length of substituted group in all cell lines tested. However, there was good correlation between the CC(50) and the log P, or molecular size in all cell lines used. Surface and volume calculated by this method are useful in evaluating the cytotoxicity of dihydroimidazole derivatives.