The development of novel efficient substances for anticancer chemotherapy is an important problem of medicinal chemistry. Aim. To evaluate the level of cytotoxic action of novel thiazole derivatives towards tumor cell lines of different origin. Methods. Four N acylated 2-amino-5-benzyl-1,3-thiazoles (5a-d) were synthesized by reaction of 2-amino-5-R-benzyl-1,3-thiazoles with acid chlorides in the presence of triethylamine in the dioxane medium. Anticancer screening of the synthesized thiazoles was performed by the MTT assay. Results. Thiazole derivatives were shown to exert antineoplastic activity towards different types of tumor cells. The anti-glioma and anti-melanoma selectivity of these derivatives action was demonstrated. The compound 5a was found to be the most toxic for human glioblastoma U251 cells and human melanoma WM793 cells. At the same time, the created compounds possessed low toxicity towards pseudo-normal cells. Conclusion. The novel thiazole derivative 5a was the most toxic against human glioblastoma and melanoma cells. K e y w o r d s: thiazole derivatives, 2-amino-5-benzyl-1,3-thiazoles, anticancer activity, leukemia, glioblastoma, melanoma.

The aim of the present study was to investigate the antiproliferative and proapoptotic actions of N-(5-benzyl-1,3-thiazol-2-yl)-3,5-dimethyl-1-benzofuran-2-carboxamide derivative (compound 5) in glioma cells in comparison with the actions of temozolomide (TMZ) and doxorubicin (Dox), used as positive controls. The antiproliferative activity of the compound 5, TMZ, and Dox on human glioblastoma U251 and human glioblastoma multiform T98G cells was measured using the MTT test. Western blot analysis, fluorescent microscopy, agarose gel retardation assay, flow cytometric analysis, and the DNA comet assay under alkaline conditions were carried out to study the effect of compound 5 on U251 cells. This compound showed ~20 times higher cytotoxicity toward U251 and T98G cells compared with the effects of TMZ and approximately two times higher activity than that of the Dox. Compound 5 induced apoptosis in U251 cells by PARP1 and caspase 3 cleavage mechanisms, also inducing an increase in the level of Bax and Bim proapoptotic proteins and a decrease in the level of phosho-ERK1/2 kinase. The cytotoxicity of compound 5 was associated with an increase in the production of the hydrogen peroxide and the formation of DNA single-strand breaks. This compound 5 did not intercalate into a DNA molecule. Thus, the novel thiazole derivative (compound 5) proved to be a potential antiglioma drug that showed much higher cytotoxic action on human glioma cells compared with the effects of TMZ and Dox. Its cytotoxicity is associated with apoptosis induction, production of the reactive oxygen species, and formation of DNA single-strand breaks without significant DNA intercalation.

The antimicrobial activity of 2,4-dioxothiazolidine-5-acetic acid amides and their 3-substituted analogs has been studied. The initial acid was obtained by an effective one-pot method using the reaction of thiourea with maleic anhydride in hydrochloric acid. The maximum anti-staphylococcal activity was exhibited by N-[5-(R-benzyl)thiazol-2-yl]-2-(2,4-dioxothiazolidin-5-yl)acetamides.Notes: Data in square brackets refer to the zones of partly inhibited growth; (-) no antimicrobial activity; none of the synthesized compounds were active with respect to Haffnia alvei and Candida albicans species.

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