Design, synthesis, and biological evaluation of novel Tempol derivatives as effective antitumor agents

Two series of novel Tempol derivatives T1 – T6 based on the piperidine nitroxide Tempol and phenolic acids were designed and synthesized, and their biological evaluation is also described. The chemical structure was verified by HRMS, IR, and EPR analysis. The antitumor activity was tested against two tumor cell lines (A549 and Hela cells). Simultaneously, HK-2 cells were selected to investigate cytotoxicity and selectivity of synthetic compounds to the normal cells. The antioxidant property was also studied by DPPH radical scavenging assay and hydrogen peroxide-induced cell injury assay. The results demonstrated that most of the Tempol derivatives exhibited more active antioxidant activity than Tempol, and all synthesized Tempol derivatives exhibited more potent antitumor activity than Tempol. Among them, compound T6 displayed the highest antitumor activity (IC 50 = 29.4 µg/mL for A549 cells; IC 50 = 16.2 µg/mL for Hela cells). The results indicated that T6 exhibited efficient antitumor performance, having the potential of being excellent antitumor agents for cancer treatment.