Synthesis and Cytotoxic Activity of Ethyl 2-Amino-1-Benzamido-4-Oxo-5-(2-Oxo-2-Arylethylidene)-4,5-Dihydro-1H-Pyrrole-3-Carboxylates

被引：4

作者：

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
]}

机构：

[1] Perm Fed Penal Serv Inst, 125 Karpinskogo St, Perm 614012, Russia

[2] Kazan State Med Univ, 49 Butlerova St, Kazan 420012, Tatarstan, Russia

[3] Perm State Pharmaceut Acad, 2 Polevaya St, Perm 614009, Russia

来源：

PHARMACEUTICAL CHEMISTRY JOURNAL | 2016年 / 49卷 / 12期

基金：

俄罗斯科学基金会;

关键词：

ethyl 2-amino-1-benzamido-4-oxo-5-(2-oxo-2-arylethylidene)-4,5-dihydro-1H-pyrrole-3-carboxylates; acute toxicity; cytotoxicity; gastrointestinal stromal tumors (GISTs); leiomyosarcoma; osteosarcoma; chemotherapy; drug resistance;

D O I：

10.1007/s11094-016-1378-1

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.).

引用

页码：817 / 820

页数：4