Synthesis and Biological Activity of 2-amino-1-aryl-5-(3,3-dimethyl-2-oxobutylidene)-4-oxo-N-(thiazol-5-yl)-4,5-dihydro-1h-pyrrole-3-carboxamides

Autor:	N. M. Igidov, M. A. Kiselev, A. V. Zakhmatov, S. S. Zykova, Pavel Dunaev, Sergei Boichuk, I. A. Rodin, I. N. Chernov, A R Galembikova, R R Khusnutdinov
Rok vydání:	2018
Předmět:	Pharmacology 010405 organic chemistry Chemistry Stereochemistry Aryl Biological activity 01 natural sciences 0104 chemical sciences 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Paclitaxel 030220 oncology & carcinogenesis Drug Discovery medicine Cytotoxic T cell Trolox Mitotic catastrophe Etoposide Acetamide medicine.drug
Zdroj:	Pharmaceutical Chemistry Journal. 52:198-204
ISSN:	1573-9031 0091-150X
DOI:	10.1007/s11094-018-1790-9
Popis:	A series of new 2-aminopyrrole derivatives [2-amino-1-aryl-5-(3,3-dimethyl-2-oxobutylidene)-4-oxo-N-(thiazol-5-yl)-4,5-dihydro-1H-pyrrole-3-carboxamides IIa-h] were synthesized via the reaction of 4-arylamino-2-tert-butyl-2,5-dihydro-5-oxofuran-2-ylacetates (Ia-h) with 2-cyano-N-(thiazol-2-yl)acetamide in the presence of Et3N. Studies of the biological activity of the synthesized compounds found that they possessed low toxicity and that 2-amino-1-(2-bromophenyl)-5-(3,3-dimethyl-2-oxobutylidene)-4-oxo-N-(thiazol-5-yl)-4,5-dihydro-1H-pyrrole-3-carboxamide (IIb) and 2-amino-1-(2,4-dichlorophenyl)-5-(3,3-dimethyl-2-oxobutylidene)-4-oxo-N-(thiazol-5-yl)-4,5-dihydro-1H-pyrrole-3-carboxamide (IIg) exhibited radical-binding activity greater than that of trolox and cytotoxic activity against gastrointestinal stromal tumor (GIST) cells, including those resistant to the target drug imatinib (Glivec). The cytotoxic activity of the synthesized compounds was comparable with that of doxorubicin chemotherapeutics and exceeded significantly those of etoposide, paclitaxel, and hydroxyurea. Apossible molecular mechanism of action of the synthesized compounds might be their ability to disrupt cell division and induce selective accumulation of M-phase cells with subsequent death by a mitotic catastrophe pathway.
Databáze:	OpenAIRE
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