Hydantoin derivatives: Harnessing antitumor and immunomodulation potential

Summary. Hydantoin and its newly synthesized derivatives have been the focus of research due to their numerous biological activities and emerging beneficial effects in various pathological conditions, including cancer. Their primary clinical use is for the treatment of epilepsy and cardiac arrhythmias, but hydantoin derivatives have also shown significant anti-inflammatory and antitumor potential. One of its most prominent antitumor properties is high antiproliferative potential against various cancer cell lines. Through various studies over the past decades, different series of hydantoin derivatives have shown antiproliferative activity with varying degrees of apoptosis in cancer cells. Different series of derivatives significantly decreased cell survival and caused a reduction in oxidative stress parameters in treated cells, indicating their significant antioxidant effects. The cell migration index was significantly decreased after treatment with different hydantoin derivatives, suggesting an inhibitory role in various processes of cancer cell motility and invasion, which are crucial for tumor invasion. An important feature of tumor progression is chronic inflammatory response, propagated by immune cells that activate pro-inflammatory genes and cytokines. Certain hydantoin derivatives reduce the expression of pro-inflammatory genes and pro-inflammatory cytokines related to carcinogenesis and tumor growth, suggesting that some hydantoin compounds possess significant anti-inflammatory effects, which could be an additional mechanism behind their antitumor effects. The results of various studies show that some of the investigated compounds from different synthetic series have the potential to be used as new chemotherapeutic agents against the growth and progression of cancers in different tumor types.