Synthesis and Cytotoxic Activity of Ethyl 2-Amino-1-Benzamido-4-Oxo-5-(2-Oxo-2-Arylethylidene)- 4,5-Dihydro-1H-Pyrrole-3-Carboxylates
- Authors: Zykova S.S.1, Galembikova A.R.2, Ramazanov B.R.2, Odegova T.F.3, Igidov N.M.3, Kiselev M.A.3, Boichuk S.V.2
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Affiliations:
- Perm Federal Penal Service Institute
- Kazan State Medical University
- Perm State Pharmaceutical Academy
- Issue: Vol 49, No 12 (2016)
- Pages: 817-820
- Section: Article
- URL: https://journals.rcsi.science/0091-150X/article/view/244299
- DOI: https://doi.org/10.1007/s11094-016-1378-1
- ID: 244299
Cite item
Abstract
Recyclization of 5-aryl-2,3-dihydro-2-furandione 3-benzoylhydrazones (I) induced by cyanoacetic ester produced ethyl 2-amino-1-benzamido-4-oxo-5-(2-oxo-2-arylethylidene)-4,5-dihydro-1H-pyrrole-3-carboxylates (IIa-g). The biological activity of the synthesized compounds, which possessed low toxicities, was investigated. Ethyl 2-amino-1-benzamido-5-[2-(4-chlorophenyl)-2-oxoethylidene]-4-oxo-4,5-dihydro-1H-pyrrole-3-carboxylate (IIf) and the 5-[2-(3,4-dimethoxyphenyl)-2-oxoethylidene] analog (IIc) exhibited the greatest cytotoxicities against several connective-tissue tumor cell lines, namely, gastrointestinal stromal tumors (GISTs), osteosarcoma U2OS, and leiomyosarcoma SK-LMS-1. Ethyl 2-amino-1-benzamido-4-oxo-5-[2-oxo-2-(p-tolyl)ethylidene]-4,5-dihydro-1H-pyrrole-3-carboxylate (IIa) suppressed significantly tumor growth of GIST, LMS, and OS cell lines. Its activity against GIST cells at 10 μM was comparable with that of imatinib (1 μM) and, at lower concentrations (2.5 and 5 μM), with those of doxorubicin (0.25 μg/mL) and etoposide (40 μM), and exceeded significantly those of taxol (1 μM) and hydroxyurea (1 mM). The cytotoxicities of most of the studied compounds at 10 μM against SK-LMS-1 and U2OS cells in vitro were significantly greater than all reference drugs (doxorubicin, taxol, etoposide, etc.).
About the authors
S. S. Zykova
Perm Federal Penal Service Institute
Author for correspondence.
Email: zykova.sv@rambler.ru
Russian Federation, 125 Karpinskogo St., Perm, 614012
A. R. Galembikova
Kazan State Medical University
Email: zykova.sv@rambler.ru
Russian Federation, 49 Butlerova St., Kazan, Tatarstan, 420012
B. R. Ramazanov
Kazan State Medical University
Email: zykova.sv@rambler.ru
Russian Federation, 49 Butlerova St., Kazan, Tatarstan, 420012
T. F. Odegova
Perm State Pharmaceutical Academy
Email: zykova.sv@rambler.ru
Russian Federation, 2 Polevaya St., Perm, 614009
N. M. Igidov
Perm State Pharmaceutical Academy
Email: zykova.sv@rambler.ru
Russian Federation, 2 Polevaya St., Perm, 614009
M. A. Kiselev
Perm State Pharmaceutical Academy
Email: zykova.sv@rambler.ru
Russian Federation, 2 Polevaya St., Perm, 614009
S. V. Boichuk
Kazan State Medical University
Email: zykova.sv@rambler.ru
Russian Federation, 49 Butlerova St., Kazan, Tatarstan, 420012