EFFECTS OF NEW DERIVATIVES OF 2-AMINO-5-BENZYLTHIAZOLE ON GENOTOXICITY AND ACUTE TOXICITY IN ALLIUM BIOASSAY

Abstract

We have found that new derivatives of 2-amino-5-benzylthiazole possess cytotoxic action towards human tumor cells (Finiuk et al., Biopolym. Cell, 2017; Finiuk et al., Ukr. Biochem. J., 2018). A release of the chemotherapeutic drugs into the environment may cause adverse effects towards ecosystems. To promote further these derivatives as potential anticancer agents, it was necessary to evaluate their genotoxicity and acute toxi­city, namely in plants that have an important trophic level in ecosystems. To do that, we used towards plant bioassays for new derivatives of N-(5-benzyl-1,3-thiazol-2-yl)-3,5-dimethyl-1-benzofuran-2-carboxamide (compound 1) and 2,8-dimethyl-7-(3-trifluoromethyl-benzyl)pyrazolo[4,3-e]thiazolo[3,2-a]pyrimidin-4-one (compound 2). Allium cepa ana-telophase assay was applied to monitor the genotoxicity of the studied compounds. Besides, the acute toxic effects such as inhibition of cell division, seed germination and growth of Allium roots were estimated. The compound 1 (10 mM) in concentration equal to the IC₅₀ for tumor cells, and compound 2 in 1 mM (1´ concentration, equal to the IC₅₀ for tumor cells) and 10 mM (10´ concentration) did not possess acute toxicity towards Allium cepa. A significant inhibition of root growth and seed germination effects were detected at using the compound 1 only in dose that is 10 times higher than the IC₅₀ for tumor cells. The ana-telophase assay did not reveal the genotoxic effect of the compounds 1 (10 mM) and 2 (1 and 10 mM). The compounds 1 (10 mM) and 2 (1 and 10 mM) did not affect the mitotic and phase (prophase, metaphase, anaphase, telophase) indices. A commercial anticancer drug Doxorubicin (0.1 and 1 mM) possessed a significant inhibitory effect on root growth and seed germination, mitotic index and enhanced a level of chromosomal aberrations in Allium cepa. The compound 1 at 10 mM and compound 2 at 1 mM and 10 mM did not possess a significant acute toxicity (inhibition of cell division, seed germination and growth of Allium roots), did not demonstrated the genotoxic effects (induction of chromosomal aberrations) in Allium bioassay. These results give primary evidence about a possibility of using the synthetic 2-amino-5-benzylthiazole derivatives – compounds 1 and 2 – as novel antineoplastic agents that will have no negative side effects in the treated plant organism. Additional experiments should be performed in order to evaluate the adverse effects of new derivatives of 2-amino-5-benzylthiazole in a vide spectrum of the concentrations for the prediction of environmental toxicity and genotoxicity of chemicals.