QSAR studies on the mechanism of radioprotection by Hoechst 33258 analogues

The factors responsible for radioprotection by Hoechst 33258 analogues have been investigated in this work. Two mechanisms likely to be operative in the radioprotecting behavior of Hoechst 33258 derivatives have been investigated. The first involves the quenching of the DNA radicals formed by the removal of an electron by the ionizing radiation, and the second is hydrogen donation at the site of hydrogen removal by the ionizing radiation. The former has been gauged from the ionization potential. Structure-activity relationships have been deduced between the ionization potentials and Brown's σp+ parameters, as well as the inductive and resonance component, for a series of analogues. It is found that there is good correlation with the σp+ parameter, as well as the resonance parameter, indicating that these substituent effects are governed mainly by the resonance effect. Electron donating substituents at the para position of the phenol ring favor enhanced radioprotecting ability. The second component has been investigated by analyzing the structure-activity relationships between the N-H bond lengths and bond orders and the substituent parameters. Again, satisfactory relationships have been deduced for the resonance parameters, and electron-donating substituents are found to weaken the benzimidazole N-H bonds, enhancing radioprotection ability.