Tetranuclear dimethyltin(IV)-cinnamate complexes with a ladder-type Sn4O4 cluster: synthesis, crystal structures, and anticancer activity

To overcome the limitations of conventional organotin-based anticancer agents, five novel dimethyltin cinnamate complexes ( C1–C5 ) were designed and synthesized by conjugating a diorganotin core with the natural product cinnamic acid moiety. All complexes were thoroughly characterized, which confirmed a common tetranuclear Sn 4 O 4 cluster structure. The tetranuclear tin core is stabilized by µ 3 -O, which serves as pivotal linkers between the metal centers, ultimately giving rise to a characteristic ladder-like Sn-O framework. Hirshfeld surface analysis of complex C1 indicated dominant H···H contacts (63.3%) in its crystal packing. Notably, the representative complex C1 exhibited exceptional stability under simulated physiological conditions. In vitro antiproliferative assays revealed that these complexes possess significant cytotoxic potency against various cancer cell lines, markedly outperforming the clinical reference drug cisplatin. Specifically, C1 demonstrated the most potent activity against HepG2 hepatocellular carcinoma cells, yielding a remarkably low IC 50 = 1.86 ± 0.88 µM. Mechanistic investigations revealed that C1 effectively binds to ct‑DNA via classical intercalation, suggesting that DNA is a potential intracellular target. Furthermore, subsequent cell-based assays demonstrated that C1 induces G2/M phase arrest and triggers apoptosis, consistent with a multi-faceted mechanism of action commonly observed for organotin(IV) anticancer agents. Collectively, these findings confirm C1 as a high-activity lead complex for the design of innovative metallodrugs targeting cancer.