Anti-cancer effects of bis-oxidized thiopyran derivatives on non-small cell lung cancer: rational design, synthesis, and activity evaluation

The development of small molecule anti-tumor drugs has emerged as a promising strategy for cancer treatment, meanwhile the EGFR is associated with tumor formation and progression. In this paper, we designed, synthesized and obtained a series of novel bis-oxidized thiopyran derivatives, and the compound S-16 was identified as the most promising compound for treating NSCLC. A series of experiments (cell cycle, apoptosis assays, in vitro/in vivo animal model and western blotting) were performed to investigate the anti-tumor mechanisms of S-16. The results indicated that S-16 could inhibit A549, H1975 and MCF-7 cancer cells (IC50 of 4, 3.14 and 0.62 mu M, respectively), block the cell cycle of H1975 in the G0/G1 phase and induce apoptosis with dose-dependent effects. What is more, the toxicity of S-16 was estimated using the hemolytic test in vitro and H&E staining and blood biochemical analysis in vivo. In addition, H1975 xenograft tumor-bearing BALB/c nude mice were established to evaluate the antitumor activity in vivo, and the results showed that a dose of 80 mg kg-1 of S-16 could inhibit 46.07% tumor growth. These data suggest that S-16 exhibited strong in vitro and in vivo antitumor activity. The molecular docking results also showed that S-16 had a high binding affinity for the EGFR protein. In conclusion, the results of this study suggest that S-16 could be a potential anti-tumor drug for targeting the EGFR. A series of bis-oxidized thiopyran derivatives were designed, synthesized and evaluated for their activity against 4 cancer cell lines.