New diarylamides and diarylureas possessing 8-amino(acetamido) quinoline scaffold: Synthesis, antiproliferative activities against melanoma cell lines, kinase inhibition, and in silico studies

被引:28
作者
Koh, Eun Jeong [1 ,2 ]
El-Gamal, Mohammed I. [3 ,4 ,6 ]
Oh, Chang-Hyun [3 ,4 ]
Lee, So Ha [1 ]
Sim, Taebo [1 ]
Kim, Garam [5 ]
Choi, Hong Seok [5 ]
Hong, Jun Hee [5 ]
Lee, Sang-gi [2 ]
Yoo, Kyung Ho [1 ]
机构
[1] Korea Inst Sci & Technol, Chem Kinom Res Ctr, Seoul 130650, South Korea
[2] Ewha Womans Univ, Dept Chem & Nano Sci BK21, Seoul 120750, South Korea
[3] Korea Inst Sci & Technol, Ctr Biomat, Seoul 130650, South Korea
[4] Univ Sci & Technol, Dept Biomol Sci, Taejon 305333, South Korea
[5] Chosun Univ, Coll Pharm, Kwangju 501759, South Korea
[6] Univ Mansoura, Fac Pharm, Dept Med Chem, Mansoura 35516, Egypt
关键词
Antiproliferative activity; Diarylamide; Diarylurea; ERK kinase; Melanoma; Quinoline; DERIVATIVES; DESIGN; DISCOVERY; DIAGNOSIS; THERAPY; BRAF;
D O I
10.1016/j.ejmech.2013.06.060
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Synthesis of a new series of diarylureas and diarylamides possessing 4-aryl-8-amino(acetamido)quinoline scaffold is described. Their in vitro antiproliferative activities against ten melanoma cell lines were tested. Compounds 11, 21, 3c, and 4c showed the highest potency against A375P cell line with IC50 values in sub-micromolar scale. Compound 4c was equipotent to Vemurafenib against A375P. In addition, compounds 11, 2a, and 21 showed high potency over the NCI-9 tested melanoma cell line panel. The IC50 values of compounds 11 and 21 were in 2-digit nanomolar scale over four and five cell lines, respectively. Compound 21 showed high, dose-dependent inhibition of ERK kinase. ADME profiling showed that compounds 11, 21, 3c, 4c, and 5b are estimated to be orally bioavailable. (C) 2013 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码:10 / 21
页数:12
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