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Synthesis and in vitro anticancer potential of new thiazole-containing derivatives of rhodanine

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Chemistry of Heterocyclic Compounds Aims and scope

New 1,3-thiazol-2-yl-, 1,3-thiazol-4-yl-, and 1,3-thiazol-5-yl-containing derivatives of N-arylalkyl- and N-carboxyalkyl-substituted rhodanines were synthesized via Knoevenagel condensation and tested against 60 cancer cell lines of NCI panel. Among these compounds, N-[2-(4-methoxyphenyl)ethyl], N-[2-(3,4-dimethoxyphenyl)ethyl], and N-carboxydecyl rhodanines with 1,3-thiazol-4-yl or 1,3-thiazol-5-yl fragments were the most effective agents causing growth inhibition of more than 50% of the individual lines of the panel. Their activity was characterized by calculated mean values of 50% growth inhibition (GI50), total growth inhibition (TGI), and 50% cell killing (LC50). For sensitive cell lines of the total panel, mean GI50 and mean TGI were similar for compounds bearing N-[2-(4-methoxyphenyl) ethyl] and N-[2-(3,4-dimethoxyphenyl)ethyl] substituents, and significantly lower for compound with N-carboxydecyl substituent. The increase in the activity of the 1,3-thiazol-5-yl-containing derivative of N-carboxyalkyl-substituted rhodanine was accompanied by a decrease in the number of cell lines sensitive to its inhibitory effects. According to the in vitro data, some of the cancer cell lines were targeted by this compound with activity ranging from submicromolar to micromolar levels. Based on molecular docking results, the possible targets for anticancer activity of the thiazole-containing rhodanine derivatives were considered.

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We would like to thank National Cancer Institute, Bethesda, MD, USA, for in vitro evaluation of anticancer activity within the framework of Developmental Therapeutic Program and Enamine Ltd. for the material and technical support of the synthesis of compounds.

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  1. V. P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine, 1 Akademika Kukharya St, Kyiv, 02094, Ukraine

    Oleksandr V. Los, Vitalii O. Sinenko, Oleksandr L. Kobzar, Victor V. Zhirnov, Andriy I. Vovk & Volodymyr S. Brovarets

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  1. Oleksandr V. Los
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  2. Vitalii O. Sinenko
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  3. Oleksandr L. Kobzar
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Correspondence to Volodymyr S. Brovarets.

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Published in Khimiya Geterotsiklicheskikh Soedinenii, 2023, 59(6/7), 484–493

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Los, O.V., Sinenko, V.O., Kobzar, O.L. et al. Synthesis and in vitro anticancer potential of new thiazole-containing derivatives of rhodanine. Chem Heterocycl Comp 59, 484–493 (2023). https://doi.org/10.1007/s10593-023-03220-z

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