Radical dendrimers: Synthesis, anti-tumor activity and enhanced cytoprotective performance of TEMPO free radical functionalized polyurethane dendrimers

Abstract Polyurethane dendrimers up to fourth generation, functionalized with stable 4-hydroxy-2, 2, 6, 6-tetramethylpiperidin-1-yloxyl (4-hydroxy TEMPO), were prepared via a single-step urethane interchange reaction and their structures were confirmed by NMR, FT-IR, MALDI-TOF MS and SEC-MALLS techniques. The terminal TEMPO radicals of the dendrimers exhibited a triplet with nitrogen hyperfine splitting constant of 14.4 G, at g = 2.0026 in the EPR spectrum and their paramagnetic nature were confirmed by vibrating sample magnetometer. The MTT assay results revealed that the G4 dendrimer had significant anti-tumor activity in A549 lung adenocarcinoma cells and this dendrimer was found not induced any cell death in normal L132 lung cells. Further, antioxidant effect of G4 dendrimer was evaluated in normal L132 lung cells; the in-vitro studies include cell morphological studies, measurement of total intracellular reactive oxygen species (ROS) using H2DCF dye and analysis of SOD, CAT, GSH and GPx. This study demonstrated the efficacy of the dendrimers through decrease in free radicals and confirmed their enhanced cytoprotective performance over N-acetyl cysteine standard used.