Tag Archives: 4-thiazolidinones

The influence of novel 4-thiazolidinone derivaties in cytoprotective mechanisms of small intestine under nsaid-induced damage

I. I. Ilkiv, R. B. Lesyk, O. Ya. Sklyarov

Danylo Halytsky Lviv National Medical University, Lviv, Ukraine;
e-mail: ira9ilkiv@gmail.com

The aim of investigation was to compare the action of novel 4-thiazolidinone derivaties (compounds Les-5054 and Les-5055) toward parameters of nitroso-oxidative processes in mucous membrane of small intestine (MMSI) in rats on the background of indomethacin induced injury. The activity of nitric oxide synthases, myelopeoxidase, content of NO, and parameters of lipoperoxidation processes were measured in MMSI and the level of H2S and L-arginine in blood serum. Administration of indomethacin caused significant destructive damages in distal part of small intestine and increase in activity of inducible nitric oxide synthase (iNOS) and intensity of lipoperoxidation  processes in comparison to control were observed. Also indomethacin injection was accompanied by decrease of H2S and L-arginine level in blood serum. Administration of 4-thiazolidinone derivaties on the background of indomethacin induced injury reduce the activity of iNOS, myeloperoxidase, intensity of lipid peroxidation and increase generation of H2S, that may be linked with the structure of this compounds. However compound Les-5054 showed more significant cytoprotective effect and antioxidant properties than compound Les-5055. Thus, the novel 4-thiazolidinone derivaties led to reduce of nitroso-oxidative processes caused by administration of NSAIDs.

Study of antineoplastic action of novel isomeric derivatives of 4-thiazolidinone

V. V. Chumak1,2, М. R. Fil’2, R. R. Panchuk2, B. S. Zimenkovsky3,
D. Ya. Havrylyuk3, R. B. Lesyk3, R. S. Stoika1,2

1Ivan Franko Lviv National Univesity, Ukraine;
2Institute of Cell Biology, National Academy of Sciences of Ukraine, Lviv;
3Danylo Halytsky Lviv National Medical University, Ukraine;
e-mail: virachumak@gmail.com

Pyrazole- and aryl-substituted derivatives of 4-thiazolidinone belong to a perspective group of compounds with potential antitumor action. Earlier, we have demonstrated high toxicity in vitro of several 4-thiazolidinones derivatives towards tumor cell lines. To further enhance the antitumor activity of novel 4-thiazolidinones, their chemical scaffold was optimized, and new pyrazole-thiazolidinones were synthesized. That allowed us to combine in one molecule the potential pharmacophore centres of previously tested compounds. As a result, “hybrid” 4-thiazolidinones exhibit higher toxicity in vitro toward tumor cells of various origin. The molecular mechanisms of antineoplastic activity of these compounds and intensity of induction of apoptosis strongly depended on the position of the substituent in the thiazolidinone cycle. In particular, Les-3661 compound, containing pyrazoline fragment in the 4th position of thiazolidinone core, exhibits 14 times higher cytotoxic activity towards tumor cells (LC50 = 3 µM) in comparison to its 2-substituted isomer Les-3713 (LC50 = 42 µM). It is demonstrated that in terms of underlying molecular mechanisms for cytotoxic effect the Les-3661 compound induced caspase-8 and caspase-9 dependent mixed-type of apoptosis, while Les-3713 induced apoptosis mediated only by the caspase-8.