Quantitative structure-activity relationship analysis of 4-trifluoromethylimidazole derivatives with the concept of absolute hardness.
Mariko Ishihara, Masami Kawase, Hiroshi Sakagami · PubMed · 2008
A semiempirical molecular-orbital method (CAChe) was applied to delineate the relationship between the cytotoxicity (evaluated by 50% cytotoxic concentration, CC50) of thirteen 4-trifluoromethylimidazole derivatives and thirteen chemical descriptors derived by the CONFLEX/PM3 method. There was a highly significant relationship between CC50 and absolute electron negativity (chi). When the CC50 was plotted vs. the octanol-water distribution coefficient (log-P), a parabolic curve was produced, with a maximum cytotoxicity (or the least CC50 value) at log-P of 4.4. On the other hand, there was no significant relationship between CC50 and heat of formation, stability of hydration, dipole moment, ionization potential, energy of highest occupied moleculer orbital (E(HOMO)), molecular weight, or absolute hardness (eta). The present study demonstrates that the biological activity of 4-trifluoromethylimidazole derivatives can be estimated by an eta-chi activity diagram.