Theoretical studies on the mechanism of radioprotection by Hoechst 33258 derivatives

Abstract

The mechanisms governing the radioprotection ability of Hoechst 33258 derivatives have been investigated in this work by an examination of their electronic structures using the semiempirical AM1 method. Correlation is made between the electronic properties of four Hoechst 33258 derivatives and their ability to offer radioprotection. The results indicate that the important property of these derivatives responsible for radioprotection is the ease of electron loss to a base radical, resulting in the quenching of the DNA base radicals. Donation of a hydrogen atom to the dehydrogenated DNA base may also contribute to radioprotection. Hydrogen atom loss occurs preferentially from the nitrogen of the benzimidazole ring next to the phenol ring. Subsequently the Hoechst radical may undergo dimerization, resulting in the quenching of the radicals. All these processes involve the phenol end of Hoechst 33258, which is electron rich. Different substituents on this ring should bring about modifications in the radioprotection abilities. These differences have been satisfactorily explained in this work. These findings should be crucial in investigating the behaviour of new proposed radioprotectors.