Bioactivity prediction and synthesis of new 3-substituted 5-thiazolylmethylene rhodanines

1Kobzar, OL
2Hodyna, DM
Sinenko, VO
1Kovalishyn, VV
Trokhimenko, OP
Slivchuk, SR
Muzychka, OV
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
Section: Chemistry
Language: Ukrainian

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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