TY - JOUR
T1 - New diarylamides and diarylureas possessing 8-amino(acetamido)quinoline scaffold
T2 - Synthesis, antiproliferative activities against melanoma cell lines, kinase inhibition, and in silico studies
AU - Koh, Eun Jeong
AU - El-Gamal, Mohammed I.
AU - Oh, Chang Hyun
AU - Lee, So Ha
AU - Sim, Taebo
AU - Kim, Garam
AU - Choi, Hong Seok
AU - Hong, Jun Hee
AU - Lee, Sang Gi
AU - Yoo, Kyung Ho
N1 - Funding Information:
This research was supported by Korea Institute of Science and Technology (KIST) and Fundamental R&D Program for Core Technology of Materials funded by the Ministry of Knowledge Economy, Republic of Korea (K0006028). We would like to thank the National Cancer Institute (NCI), Bethesda, Maryland, USA, for performing the anticancer testing over nine melanoma cell line panel.
PY - 2013
Y1 - 2013
N2 - 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 1l, 2l, 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 1l, 2a, and 2l showed high potency over the NCI-9 tested melanoma cell line panel. The IC50 values of compounds 1l and 2l were in 2-digit nanomolar scale over four and five cell lines, respectively. Compound 2l showed high, dose-dependent inhibition of ERK kinase. ADME profiling showed that compounds 1l, 2l, 3c, 4c, and 5b are estimated to be orally bioavailable.
AB - 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 1l, 2l, 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 1l, 2a, and 2l showed high potency over the NCI-9 tested melanoma cell line panel. The IC50 values of compounds 1l and 2l were in 2-digit nanomolar scale over four and five cell lines, respectively. Compound 2l showed high, dose-dependent inhibition of ERK kinase. ADME profiling showed that compounds 1l, 2l, 3c, 4c, and 5b are estimated to be orally bioavailable.
KW - Antiproliferative activity
KW - Diarylamide
KW - Diarylurea
KW - ERK kinase
KW - Melanoma
KW - Quinoline
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U2 - 10.1016/j.ejmech.2013.06.060
DO - 10.1016/j.ejmech.2013.06.060
M3 - Article
C2 - 24128410
AN - SCOPUS:84885358486
VL - 70
SP - 10
EP - 21
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
SN - 0223-5234
ER -