New triarylpyrazoles as broad-spectrum anticancer agents: Design, synthesis, and biological evaluation

被引：25
作者：
El-Gamal, Mohammed I. [1 ,2 ,3 ]
Park, Yi Seul [1 ,4 ]
Chi, Dae Yoon [4 ]
Yoo, Kyung Ho [5 ]
Oh, Chang-Hyun [1 ,2 ]
机构：
[1] Korea Inst Sci & Technol, Ctr Biomat, Seoul 130650, South Korea
[2] Univ Sci & Technol, Dept Biomol Sci, Taejon 305333, South Korea
[3] Univ Mansoura, Fac Pharm, Dept Med Chem, Mansoura 35516, Egypt
[4] Sogang Univ, Dept Chem, Seoul 121742, South Korea
[5] Korea Inst Sci & Technol, Chem Kin Res Ctr, Seoul 130650, South Korea
来源：
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2013年 / 65卷
关键词：
Anticancer; Cytotoxicity; Diarylurea; Diarylamide; 1,3,4-Triarylpyrazole; MELANOMA-CELL LINE; ANTIPROLIFERATIVE ACTIVITY; 1,3,4-TRIARYLPYRAZOLE SCAFFOLD; DERIVATIVES; DIARYLAMIDES; DIARYLUREAS; DISCOVERY;
D O I：
10.1016/j.ejmech.2013.04.067
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A new series of diarylureas and diarylamides possessing 1,3,4-triarylpyrazole scaffold was designed and synthesized. Their in vitro antiproliferative activities against NCI-60 cell line panel were tested. Most of the compounds showed strong and broad-spectrum antiproliferative activities. Compound 18 exerted sub-micromolar IC50 values over all the subpanels of nine different cancer types. Its IC50 value over MDA-MB-435 melanoma cell line was 27 nM. Compounds 10-13, 22, and 23 possessing urea spacer exerted lethal effect over the NCI-60 panel with mean %inhibitions more than 100% in single-dose testing. Compounds 13 and 23 with urea linker and 3',5'-bis(trifluoromethyl)phenyl terminal ring showed the highest mean %inhibition over the NCI-60 panel in single-dose testing, and showed high potencies and broad-spectrum anticancer activities in five-dose testing. (C) 2013 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码：315 / 322
页数：8
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