Ukr.Biochem.J. 2026; Volume 98, Issue 4, Jul-Aug, pp. 96-107

doi: https://doi.org/10.15407/ubj98.04.096

Effects of pyrrolidinedione-thiazolidinone hybrid molecules on the genotoxicity in vitro

30.07.2026   Uncategorized

N. Finiuk1,2*, O. Klyuchivska1, R. Lesyk2,3, R. Stoika1

1Department of Regulation of Cell Proliferation and Apoptosis,
Institute of Cell Biology, National Academy of Sciences of Ukraine, Lviv, Ukraine;
2Molecular Design Center, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine;
3Department of Pharmaceutical, Organic and Bioorganic Chemistry,
Danylo Halytsky Lviv National Medical University, Lviv, Ukraine;
*e-mail: nataliyafiniuk@gmail.com

Received: 25 May 2026; Revised: 17 July 2026;
Accepted: 27 July 2026; Available on-line:  04 August 2026

Background. Pyrrolidinedione-thiazolidinone hybrid molecules represent a promising class of anticancer candidates; however, a comprehensive evaluation of their genotoxic and mutagenic safety profile is essential before further preclinical development. Objectives. This work aimed to investigate the genotoxic potential of pyrrolidinedione-thiazolidinone hybrid molecules Les-6287 and Les-6294 that possessed antineoplastic activity. Methods. The mutagenic potential was evaluated using the Ames bacterial reverse mutation test with Salmonella typhimurium strains TA98 and TA100 in the presence and absence of metabolic activation (S9 fraction). The effects at the chromosomal level were assessed using the Allium cepa anaphase-telophase chromosome aberration assay. Primary DNA strand break induction was quantified using the alkaline comet assay. Results. Les-6287 and Les-6294 at 10 and 100 µM concentrations do not produce a mutagenic activity exceeding 1.6 in either S. typhimurium strain TA98 or TA100, with or without S9-mediated metabolic activation. In the A. cepa anaphase-telophase assay treatment with Les-6287 and Les-6294 did not result in a statistically significant elevation in chromosomal aberration frequency relative to the negative control (2.8%), with observed values ranging from 3.3% to 4.3% across all tested concentrations. No significant alterations in the mitotic index were recorded. The alkaline comet assay revealed no significant increase in primary DNA damage, with percent tail DNA of 1.3-1.9% in treated peripheral blood mononuclear cells. Conclusion. Pyrro­lidinedione-thiazolidinone hybrid molecules Les-6287 and Les-6294 at concentrations up to 100 µM do not pose a genotoxic or mutagenic risk under the tested experimental conditions. Further targeted safety assessments are needed prior to progressing Les-6287 and Les-6294 to preclinical evaluation as candidate antitumor agents.

Keywords: , , , ,

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