Synthesis of 5-arylidene-2-amino-4-azolones and evaluation of their anticancer activity

被引：95

作者：

Subtel'na, Ivanna ^{[1
]}

Atamanyuk, Dmytro ^{[1
]}

Szymanska, Ewa ^{[2
]}

Kiec-Kononowicz, Katarzyna ^{[2
]}

Zimenkovsky, Borys ^{[1
]}

Vasylenko, Olexandr ^{[3
]}

Gzella, Andrzej ^{[4
]}

Lesyk, Roman ^{[1
]}

机构：

[1] Danylo Halytsky Lviv Natl Med Univ, Dept Pharmaceut Organ & Bioorgan Chem, UA-79010 Lvov, Ukraine

[2] Jagiellonian Univ, Coll Med, Dept Technol & Biotechnol Drugs, PL-30688 Krakow, Poland

[3] Natl Acad Sci Ukraine, Inst Bioorgan Chem & Petrochem, UA-02094 Kiev, Ukraine

[4] Karol Marcinkowski Poznan Univ Med Sci, Dept & Chair Organ Chem, PL-60780 Poznan, Poland

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2010年 / 18卷 / 14期

关键词：

5-Arylidene-2-amino-4-azolones; Synthesis; X-ray studies; Anticancer activity; SAR; COMPARE analysis; 5-ARYLIDENE AROMATIC DERIVATIVES; GRAPH-SET ANALYSIS; CANCER CELL-LINES; ANTIPROLIFERATIVE ACTIVITY; ANTIMYCOBACTERIAL ACTIVITY; RHODANINE DERIVATIVES; BIOLOGICAL EVALUATION; ANTITUMOR-ACTIVITY; INHIBITORS; HYDANTOIN;

D O I：

10.1016/j.bmc.2010.05.073

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Series of novel 5-arylidene-2-arylaminothiazol-4(5H)-ones and 2-aryl(benzyl)amino-1H-imidazol-4(5H)ones were synthesized from appropriate 2-alkylthioazol-4-ones using nucleophilic substitution in position 2 by various anilines and benzylamines and Knoevenagel reaction. X-ray structural studies of 22 revealed the structure to be intermediate between amino and imino tautomeric forms. All the target compounds were evaluated for the anticancer activity in vitro in standard National Cancer Institute 60 cancer cell lines assay. Majority of compounds showed significant antitumor cytotoxicity effect at micromolar and submicromolar level (Mean Log GI(50) ranges -5.77 to -4.35). Some of the most potent compounds, namely 10 and 13, possessed selectively high effect on all leukemia cell lines at submicromolar level (Mean Log GI50 [leukemia lines], respectively, -6.41 and -6.29), which are probably associated with immunosuppressive activity. Individual cancer cell lines sensitivity to synthesized compounds and SAR studies are discussed. COMPARE analysis allowed to disclose probable modes of anticancer action for synthesized compounds, in particular showed number of high correlations with activity patterns of alkylating agents (PCC similar to 0.606-0.731). (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：5090 / 5102

页数：13

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