Antineoplastic activity of novel thiazole derivatives

Abstract

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.

Effects of thiazole derivatives on intracellular structure and functions in murine lymphoma cells

“…were synthetized by reaction of 2-amino-5-R-benzyl-1,3-thiazoles with acid chlorides in the presence of triethylamine in dioxane medium at the Chemistry Faculty of Ivan Franko National University of Lviv, Ukraine as previously described [5,8]. Stock solutions of the tested compounds were prepared in dimethyl sulfoxide (DMSO, Sigma-Aldrich, St. Louis, USA).…”

“…introduction Thiazole derivatives are attractive heterocycles for pharmaceutical and medicinal chemists who design new potent anticancer agents [1][2][3][4]. It was shown that two novel thiazole derivatives -N-(5-benzyl-1,3-thiazol-2-yl)-3,5-dimethyl-1-benzofuran-2-carboxamide (BF1) and 7-benzyl-8-methyl-2-propylpyrazolo[4,3-e]thiazolo [3,2-a] pyrimidin-4(2H)-one (PP2) [5] have a high cytotoxic effect toward various cancer cell lines, such as glioblastoma (U251 and T98G) and human myeloid leukemia (HL 60 and K562) [6,7]. These compounds also had low toxicity towards human kidney cells (HEK 293) and human keratinocytes (HaCaT line) [5,8].…”

“…It was shown that two novel thiazole derivatives -N-(5-benzyl-1,3-thiazol-2-yl)-3,5-dimethyl-1-benzofuran-2-carboxamide (BF1) and 7-benzyl-8-methyl-2-propylpyrazolo[4,3-e]thiazolo [3,2-a] pyrimidin-4(2H)-one (PP2) [5] have a high cytotoxic effect toward various cancer cell lines, such as glioblastoma (U251 and T98G) and human myeloid leukemia (HL 60 and K562) [6,7]. These compounds also had low toxicity towards human kidney cells (HEK 293) and human keratinocytes (HaCaT line) [5,8]. Previously we have identified that BF1 increased the level of Bax and Bim pro-apoptotic proteins in glioma cells [6], and PP2 increased the level of pro-apoptotic Bim protein and the mitochondriaspecific EndoG nuclease, and decreased the level of the anti-apoptotic Bcl-2 protein in the leukemia cells in vitro [7].…”

Evaluation of antiproliferative activity of pyrazolothiazolopyrimidine derivatives

“…The aim of our study was to test the cytotoxic effects in vitro of seven novel pyrazolothiazolopyrimidine derivatives that target several mammalian tumor cell lines and for comparison, pseudo-normal cell lines. The stock solution of tested compounds (10 mM) was prepared in dimethyl sulfoxide (DMSO, Sigma-Aldrich, St. Louis, MO, USA), and before adding to the cells, further solutions were prepared using culture medium [25]. Doxorubicin (Dox, Teva, Haarlem, the Netherlands) was used as a positive control.…”

Effects of new derivatives of 2-amino-5-benzylthiazole of genotoxicity and acute toxicity in Allium bioassays

“…New thiazole derivative, namely N(5benzyl1,3thiazol2yl)3,5dimethyl1benzofuran-2-carboxamide (here noted as compound 1) demonstrated a toxicity against human glioblastoma U251 cells (IC 50 = 9.8±0.82 µM) and human melanoma WM793 cells (IC 50 = 7.2±0.48 µM) [6], while 2,8dimethyl7(3trifluoromethylbenzyl)pyra zolo [4,3e]thiazolo [3,2a]pyrimidin4one (here noted as compound 2) demonstrated a toxicity against human leukemia cells of HL60 (IC 50 was was 0.09±0.008 µM), against Jurkat and K562 lines (IC 50 was approximately 1 µM) [7]. IC 50 of compounds 1 and 2 for pseudo-normal cells was 3.2-30 µM [6,7]. Besides, it was shown that the compound 1 induced apoptosis and DNA damage, affected a transition of G2/M phase of cell cycle in human glioblastoma U251 cells [8, accepted].…”