Tag Archives: 4-thiazolidinone

Synthesis and anti-leukemic activity of pyrrolidinedione-thiazolidinone hybrids

A. Kryshchyshyn1*, D. Kaminskyy1, O. Roman1, R. Kralovics2, O. Karpenko3, R. Lesyk1

1Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, Ukraine;
2Research Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria;
3Enamine Ltd., Kyiv, Ukraine;
*e-mail: kryshchyshyn.a@gmail.com

Received: 22 December 2019; Accepted: 27 March 2020

A series of novel 2-(5-ylidene-4-oxo-2-thioxo-thiazolidin-3-yl)-succinimides and 5-ylidene-3-(1-arylpyrrolidine-2,5-dione)-thiazolidine-2,4-diones were synthesized. An efficient simple protocol for rhodanine-pyrrolidinedione hybrids synthesis which allows avoiding the step of anhydride formation was proposed. Following the previous data on antileukemic properties of related thiazolidinone derivatives, the activity of 19 target compounds was investigated towards four leukemia cell lines: Dami, HL-60, Jurkat, and K562. Among the tested compounds, 3-[5-(4-chloro-benzylidene)-4-oxo-2-thioxo-thiazolidin-3-yl]-1-phenyl-pyrrolidine-2,5-dione (Compound 1) possessed good and selective antiproliferative action against Dami and HL-60 cell lines and satisfactory toxicity level (acute toxicity evaluated in vivo in mice).

Indicators of oxidative and nitrosative stress and activity of enzymes of nitric oxide metabolism in rats treated with 4-thiazolidinone derivatives possessing antineoplastic activity

L. I. Kоbylinska1, R. R. Panchuk2, R. B. Lesyk1,
B. S. Zіmenkovsky1, R. S. Stoika2

1Danylo Halytsky Lviv National Medical University, Ukraine;
2Institute of Cell Biology, National Academy of Sciences of Ukraine, Lviv;
e-mail: lesya8@gmail.com

Principal ways of generation and function of free oxygen and nitrogen radical metabolites, as well as the ways of their bio-neutralization in rats treated with potential anticancer drugs have been discussed. Three isatin-pyrazoline 4-thiazolidinone conjugates – Les-3288, Les-3833 and Les-3882 – were selected as the most perspective antineoplastic agents. Since the reactive oxygen species (ROS) and reactive nitrogen species are responsible for negative side effects of many anticancer drugs, we measured the indicators of the oxidative and nitrosative stress and the activity of enzymes of the nitric oxide metabolism in blood of rats treated with such compounds. It was found that both Les-3833 and doxorubicin used as a positive control increased the level of specific indicators of the oxidative and nitrosative stress, while Les-3288 and Les-3882 did not cause a significant elevation in ROS content. There were no big changes in the activity of either iNO-synthase or NO-reductase under the action of doxorubicin, while Les-3288 and Les-3882 induced a decrease in the activi­ty of iNO-synthase, and Les-3288 induced a decrease in the activity of NO-reductase. Thus, the content of low molecular weight indicators of the oxidative and nitrosative stress in blood of rats is of higher informative value than the level of activity of enzymes of the nitric oxide metabolism at the action of such toxic agents as anticancer drugs. These indicators should be used for assessment of toxic damage of tissues and organs by the anticancer drugs.