In vitro radioprotection by methylproamine

Reports of the unexpected radioprotective activity of the minor groove-binding bibenzimidazole Hoechst 33342 has prompted the development of a new DNA-binding radioprotector. Guided by the hypothesis that the radioprotective activity of Hoechst 33342 was due to electron donation, in contradistinction to the oxidative properties of electron afinic radiosensitisers, analogues of Hoechst 33342 with electron-rich substituents were synthesised. The most promising of these analogues is methylproamine, in which the ethoxy group of Hoechst 33342 is replaced by an NN-dimethylamino, with the addition of a methyl group into the phenyl ring. The impressive feature of methylproamine is its radioprotective potency in cell culture. Survival curve studies with V79 cells have demonstrated a dose modification factor of 2.1 with cells exposed to a concentration of just 30 micromolar methylproamine, before, after and during irradiation. By comparison, 100-fold higher concentrations of the classic amino thiol radioprotectors are required to confer this level of radioprotection in similar experiments reported in the literature. Analysis of the methylproamine survival curve data according to the alpha-beta model indicate that both components are modified by the radioprotector. Studies not reported here, have demonstrated radioprotective activity of methylproamine in vivo, raising the possibility of potential utility in protecting normal cells during cancer radiotherapy