Email this article 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
- Authors: Zykova S.S.1, Igidov N.M.2, Zakhmatov A.V.2, Kiselev M.A.2, Galembikova A.R.3, Khusnutdinov R.R.3, Dunaev P.D.3, Boichuk S.V.3, Chernov I.N.4, Rodin I.A.5
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Affiliations:
- Perm Federal Penitentiary Service Institute
- Perm State Pharmaceutical Academy
- Kazan State Medical University
- Research Institute of Chemistry, N. I. Lobachevsky State University of Nizhny Novgorod
- I. T. Trubilin Kuban State Agrarian University
- Issue: Vol 52, No 3 (2018)
- Pages: 198-204
- Section: Search for New Drugs
- URL: https://journals.rcsi.science/0091-150X/article/view/245076
- DOI: https://doi.org/10.1007/s11094-018-1790-9
- ID: 245076
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Abstract
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.
About the authors
S. S. Zykova
Perm Federal Penitentiary Service Institute
Author for correspondence.
Email: zykova.sv@rambler.ru
Russian Federation, 125 Karpinskogo St., Perm, 614012
N. M. Igidov
Perm State Pharmaceutical Academy
Email: zykova.sv@rambler.ru
Russian Federation, 2 Polevaya St., Perm, 614099
A. V. Zakhmatov
Perm State Pharmaceutical Academy
Email: zykova.sv@rambler.ru
Russian Federation, 2 Polevaya St., Perm, 614099
M. A. Kiselev
Perm State Pharmaceutical Academy
Email: zykova.sv@rambler.ru
Russian Federation, 2 Polevaya St., Perm, 614099
A. R. Galembikova
Kazan State Medical University
Email: zykova.sv@rambler.ru
Russian Federation, 49 Butlerova St., Kazan, Tatarstan, 420012
R. R. Khusnutdinov
Kazan State Medical University
Email: zykova.sv@rambler.ru
Russian Federation, 49 Butlerova St., Kazan, Tatarstan, 420012
P. D. Dunaev
Kazan State Medical University
Email: zykova.sv@rambler.ru
Russian Federation, 49 Butlerova St., Kazan, Tatarstan, 420012
S. V. Boichuk
Kazan State Medical University
Email: zykova.sv@rambler.ru
Russian Federation, 49 Butlerova St., Kazan, Tatarstan, 420012
I. N. Chernov
Research Institute of Chemistry, N. I. Lobachevsky State University of Nizhny Novgorod
Email: zykova.sv@rambler.ru
Russian Federation, 23/5 Prosp. Gagarina, Nizhny Novgorod, 603950
I. A. Rodin
I. T. Trubilin Kuban State Agrarian University
Email: zykova.sv@rambler.ru
Russian Federation, 13 Kalinina St, Krasnodar, 350044
