|1Kobzar, OL |
1Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Kyiv
2Institute of Macromolecular Chemistry of the NAS of Ukraine, Kyiv
|Dopov. Nac. akad. nauk Ukr. 2020, 5:70-77|
The virtual screening of a database of Z- and E-isomeric thiazole-containing derivatives of N-methyl-, N-ben zyland N-phenylethyl-substuted rhodanines is performed by regression and classification QSAR models for predicting the antiblastic activity of compounds against Hep-2 cells. The molecular docking method is used to evaluate the affinity of 3-substituted 5-thiazolylmethylene rhodanines to the ATP-binding site of potential target protein, the protein kinase Pim-1. According to the virtual screening results, ten compounds from the database were selected and synthesized by the reaction of N-substituted rhodanines with thiazol-2-carboxaldehydes, thiazol-4-carboxaldehydes and thiazol-5-carboxaldehydes. In vitro study of the compounds with N-substituted rhodanine scaffold showed the cytotoxic activity on the cell culture of human laryngeal adenocarcinoma Hep-2 which was 2.7-10 times lower in comparison with the effect of cisplatin as a reference. The results indicated that the rhodanine derivative with thiazol-2-yl and N-(4-methoxyphenyl)ethyl substituents, as well as rhodanine compound bearing thiazol-4-yl and N-4-methylbenzyl groups, exhibited the most pronounced effects. The toxicity of these compounds evaluated on hydrobiont D. magna was two orders of magnitude lower than that of cisplatin.
|Keywords: antiblastic activity, molecular docking, QSAR-analysis, rhodanines, synthesis, thiazoles|
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