Evaluation of new thiadiazoles and benzothiazoles as potential radioprotectors: Free radical scavenging activity in vitro and theoretical studies (QSAR, DFT)

Thiol and aminothiol compounds are among the most efficient chemical radio protectors. To increase their efficiency, we synthesized two new classes of thiol and aminothiol compounds derived from benzothiazole (T1, T2, AM1, AM2) and thiadiazole (T3, T4, AM3) structures. We examined them for their ability to scavenge free radicals (DPPH center dot, ABTS(center dot+), (OH)-O-center dot). Thiol derivatives with a thiadiazole structure are the most active compounds scavenging DPPH' and ABTS + free radicals, with an IC50 of 0.053 +/- 0.006 and 0.023 +/- 0.002 mM, respectively, for the derivative T3. Moreover, compounds T1, T2, and T3 at 60 mu M gave 83% protection against 2-deoxyribose degradation by (OH)-O-center dot. The ability of these compounds to protect DNA against (OH)-O-center dot produced by a Fenton reaction and gamma-irradiation (15 Gy)-induced strand breaks was also evaluated on pBR322 plasmid DNA. In both tests thiol derivatives were the most efficient compounds. Derivatives T2 and T3 totally inhibit DNA strand breaks at the concentration of 50 mu M. The protection afforded by these derivatives was comparatively higher than that of the radioprotectors WR-2721 and WR-1065. Our data indicate that these two compounds are free radical scavengers and potential antioxidant agents. Finally, DFT and QSAR studies were performed to support the experimental observations. (C) 2009 Elsevier Inc. All rights reserved.