TY - JOUR T1 - <em>In Vitro</em> Effects of Bromoalkyl Phenytoin Derivatives on Regulated Death, Cell Cycle and Ultrastructure of Leukemia Cells JF - Anticancer Research JO - Anticancer Res SP - 6373 LP - 6380 VL - 37 IS - 11 AU - KATARZYNA ŚLADOWSKA AU - MAŁGORZATA OPYDO-CHANEK AU - TEODORA KRÓL AU - WOJCIECH TRYBUS AU - EWA TRYBUS AU - ANNA KOPACZ-BEDNARSKA AU - JADWIGA HANDZLIK AU - KATARZYNA KIEĆ-KONONOWICZ AU - LIDIA MAZUR Y1 - 2017/11/01 UR - http://ar.iiarjournals.org/content/37/11/6373.abstract N2 - Background/Aim: To search for new antileukemic agents, the chemical structure of phenytoin was modified. A possible cytotoxic activity of three bromoalkyl phenytoin analogs, methyl 2-(1-(3-bromopropyl)-2,4-dioxo-5,5-diphenylimidazolidin-3-yl) propanoate (PH2), 1-(3-bromopropyl)-3-methyl-5,5-diphenylimidazolidine-2,4-dione (PH3) and 1-(4-bromobutyl)-3-methyl-5,5-diphenylimidazolidine-2,4-dione (PH4) on regulated cell death, the cell cycle and cell ultrastructure was assessed. Materials and Methods: The experiments were performed in vitro on HL-60 and U937 cells, using flow cytometry and electron microscopy methods. Results: Application of PH2, PH3, and PH4 resulted in cell surface exposure of phosphatidylserine and plasma membrane impairment, caspase-8, -9, and -3/7 activation, dissipation of mitochondrial membrane potential, DNA breakage, cell-cycle disturbance and cell ultrastructural changes. In general, PH3 appeared to be the most active against the leukemia cells, and all bromoalkyl hydantoins, PH2-PH4, were more active in HL-60 cells than in U937 cells. Conclusion: The antileukemic activity of the bromoalkyl phenytoin analogs depended on the combination of N-hydantoin substituents and the human cell line used. ER -