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


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Аннотация

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.

Авторлар туралы

S. Zykova

Perm Federal Penitentiary Service Institute

Хат алмасуға жауапты Автор.
Email: zykova.sv@rambler.ru
Ресей, 125 Karpinskogo St., Perm, 614012

N. Igidov

Perm State Pharmaceutical Academy

Email: zykova.sv@rambler.ru
Ресей, 2 Polevaya St., Perm, 614099

A. Zakhmatov

Perm State Pharmaceutical Academy

Email: zykova.sv@rambler.ru
Ресей, 2 Polevaya St., Perm, 614099

M. Kiselev

Perm State Pharmaceutical Academy

Email: zykova.sv@rambler.ru
Ресей, 2 Polevaya St., Perm, 614099

A. Galembikova

Kazan State Medical University

Email: zykova.sv@rambler.ru
Ресей, 49 Butlerova St., Kazan, Tatarstan, 420012

R. Khusnutdinov

Kazan State Medical University

Email: zykova.sv@rambler.ru
Ресей, 49 Butlerova St., Kazan, Tatarstan, 420012

P. Dunaev

Kazan State Medical University

Email: zykova.sv@rambler.ru
Ресей, 49 Butlerova St., Kazan, Tatarstan, 420012

S. Boichuk

Kazan State Medical University

Email: zykova.sv@rambler.ru
Ресей, 49 Butlerova St., Kazan, Tatarstan, 420012

I. Chernov

Research Institute of Chemistry, N. I. Lobachevsky State University of Nizhny Novgorod

Email: zykova.sv@rambler.ru
Ресей, 23/5 Prosp. Gagarina, Nizhny Novgorod, 603950

I. Rodin

I. T. Trubilin Kuban State Agrarian University

Email: zykova.sv@rambler.ru
Ресей, 13 Kalinina St, Krasnodar, 350044

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