Chumak V. Mechanisms of antineoplastic action of new heterocyclic compounds on base of 4-thiazolidinone

The thesis is devoted to the study of the mechanisms of action of new antineoplastic derivatives of 4-tiazolidynone. In the study were used 3 groups of 4-tiazolidynones: izatin and cyminal containing and "hybrid" substances containing tsyminal and 3.5 dypirazolin. The presence of halogen in the 5th position of izatin cause an increasing of cytotoxic activity of compounds compared with compounds whith nonhalohenated izatin. In the 2nd group of substances with replacement of benzyliden to cyminal shown 2-fold increasing of ID-3506 cytotoxicity, a powerful rapid generation of ROS by cells, an earlier and intense induction of apoptosis. For the first time was shown that 3.5 dypirazoline in 4th position of tiazolidynone cycle from 3rd of studied 4-tiazolidynones leads to the increasing of cytotoxicity of "hybrid" substance ID-3661 by 3-5 times compared with the effect of parent compounds and 14 times compared with its isomer ID-3713. Substance ID-3661 induces apoptosis of mixed type in contrast with apoptosis receptor by the actions of the parent compound ID-3120 and ER apoptosis by action ID-3372 in vitro, and inhibits the growth of ascites lymphoma NK/Ly in mice in vivo.