학술논문
Synthesis and Cytotoxic Activity of Ethyl 2-Amino-1-Benzamido-4-Oxo-5-(2-Oxo-2-Arylethylidene)- 4,5-Dihydro-1H-Pyrrole-3-Carboxylates
Article
Article
Document Type
Academic Journal
Author
Source
Pharmaceutical Chemistry Journal. March 2016, Vol. 49 Issue 12, p817, 4 p.
Subject
Language
English
ISSN
0091-150X
Abstract
Author(s): S. S. Zykova[sup.1] , A. R. Galembikova[sup.2] , B. R. Ramazanov[sup.2] , T. F. Odegova[sup.3] , N. M. Igidov[sup.3] , M. A. Kiselev[sup.3] , S. V. Boichuk[sup.2] Author Affiliations: [...]
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 [mu]M was comparable with that of imatinib (1 [mu]M) and, at lower concentrations (2.5 and 5 [mu]M), with those of doxorubicin (0.25 [mu]g/mL) and etoposide (40 [mu]M), and exceeded significantly those of taxol (1 [mu]M) and hydroxyurea (1 mM). The cytotoxicities of most of the studied compounds at 10 [mu]M against SK-LMS-1 and U2OS cells in vitro were significantly greater than all reference drugs (doxorubicin, taxol, etoposide, etc.).
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 [mu]M was comparable with that of imatinib (1 [mu]M) and, at lower concentrations (2.5 and 5 [mu]M), with those of doxorubicin (0.25 [mu]g/mL) and etoposide (40 [mu]M), and exceeded significantly those of taxol (1 [mu]M) and hydroxyurea (1 mM). The cytotoxicities of most of the studied compounds at 10 [mu]M against SK-LMS-1 and U2OS cells in vitro were significantly greater than all reference drugs (doxorubicin, taxol, etoposide, etc.).