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SDIRSACR Oncology Insights

P77

Cytotoxic evaluation of novel 4-oxothiazolidine derivatives on human cancer cell lines

Lena Mišić, Aleksandra M. Bondžić, Bojan P. Bondžić, Lela Korićanac, Jelena Žakula

Vinča Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, P.O. Box 522, 11000
Belgrade, Serbia
University of Belgrade-Institute of Chemistry, Technology and Metallurgy, National Institute of the Republic of Serbia, Njegoševa
12, 11000 Belgrade, Serbia

Keywords: 4-oxothiazolidine derivatives, cell survival, neoplasms

Background: 4-oxothiazolidine and its derivatives are an important class of heterocyclic compounds known for their
diverse pharmacological effects, including anticancer activity. Their low cost of synthesis, structural diversity, and
potential for selective cytotoxicity make them valuable candidates for further research. This study aimed to investigate
the in vitro cytotoxic activity of selected 4-oxothiazolidine derivatives on various cell lines.
Material and Methods: The cytotoxicity of 14 synthesized 4oxothiazolidine derivatives, divided into three groups
((1) compounds 1-6, no substituent; (2) compounds 7-10 with 2ethoxy2oxoethyl substituent; and (3) compounds 11-
14, methyl substituent) based on the substituent at position 5 of the thiazolidine ring, was assessed using the
Sulforhodamine B assay on 6 human cell lines: HeLa, HCT-116, MIA PaCa-2, PANC-1, MDA-468 cancer cells, and MRC-5
normal lung fibroblasts, 72 h after treatment.
Results: All tested compounds exhibited varying cell line-specific effects, with significant differences in both activity
and selectivity. The HCT116 cells showed an excellent response to treatment with all analyzed 4-oxothiazolidine
derivatives, with viability percentages 14.3-46.5%, except for compound 1 (73.5%). HeLa cells were particularly sensitive
to compounds 4 and 6, with approximately 10% of viable cells remaining, while they showed moderate sensitivity to
the other compounds (30-60%). Compounds 6 and 9-14 exhibited significant cytotoxic effects, reducing the viability
of MIA PaCa-2 cells to 23.5-56.1%, while all other compounds had little to no effect (70.7-92.7%). PANC-1 and MDA-
468 cells demonstrated considerable resistance to 4-oxothiazolidine derivatives, with viability of over 58% and 59.6%,
respectively. Notably, MDA-468 cells showed stimulation after treatment with compounds 1 and 6. Compound 9
exhibited the best selectivity, with 73% of fibroblasts remaining viable post- treatment.
Conclusions: The tested 4-oxothiazolidine derivatives showed cell-specific cytotoxic effects, with significant variability
in both potency and selectivity among the derivatives. Some cancer cell lines exhibited greater sensitivity to these
compounds, suggesting that their effectiveness may vary depending on specific tumor types or cellular characteristics.
In contrast, other cell lines showed moderate to low sensitivity, highlighting the importance of understanding how
these compounds interact with different cancer contexts.

Acknowledgments and funding: This study was supported by the Ministry of Science, Technological Development
and Innovation of the Republic of Serbia (contract numbers: 451-03-136/2025-03/200017 and 451-03-136/2025-
03/200026

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