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

Eun Jeong Koh; Mohammed I. El-Gamal; Chang Hyun Oh; So Ha Lee; Taebo Sim; Garam Kim; Hong Seok Choi; Jun Hee Hong; Sang Gi Lee; Kyung Ho Yoo

doi:10.1016/j.ejmech.2013.06.060

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

Eun Jeong Koh, Mohammed I. El-Gamal, Chang Hyun Oh, So Ha Lee, Taebo Sim, Garam Kim, Hong Seok Choi, Jun Hee Hong, Sang Gi Lee, Kyung Ho Yoo

Department of Chemistry & Nanoscience

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	10-21
Number of pages	12
Journal	European Journal of Medicinal Chemistry
Volume	70
DOIs	https://doi.org/10.1016/j.ejmech.2013.06.060
State	Published - 2013

Bibliographical note

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.

Keywords

Antiproliferative activity
Diarylamide
Diarylurea
ERK kinase
Melanoma
Quinoline

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10.1016/j.ejmech.2013.06.060

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Koh, E. J., El-Gamal, M. I., Oh, C. H., Lee, S. H., Sim, T., Kim, G., Choi, H. S., Hong, J. H., Lee, S. G., & Yoo, K. H. (2013). New diarylamides and diarylureas possessing 8-amino(acetamido)quinoline scaffold: Synthesis, antiproliferative activities against melanoma cell lines, kinase inhibition, and in silico studies. European Journal of Medicinal Chemistry, 70, 10-21. https://doi.org/10.1016/j.ejmech.2013.06.060

@article{89b356a715804628a9ea2a716ad859c7,

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

abstract = "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.",

keywords = "Antiproliferative activity, Diarylamide, Diarylurea, ERK kinase, Melanoma, Quinoline",

author = "Koh, {Eun Jeong} and El-Gamal, {Mohammed I.} and Oh, {Chang Hyun} and Lee, {So Ha} and Taebo Sim and Garam Kim and Choi, {Hong Seok} and Hong, {Jun Hee} and Lee, {Sang Gi} and Yoo, {Kyung Ho}",

note = "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.",

year = "2013",

doi = "10.1016/j.ejmech.2013.06.060",

language = "English",

volume = "70",

pages = "10--21",

journal = "European Journal of Medicinal Chemistry",

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Koh, EJ, El-Gamal, MI, Oh, CH, Lee, SH, Sim, T, Kim, G, Choi, HS, Hong, JH, Lee, SG & Yoo, KH 2013, 'New diarylamides and diarylureas possessing 8-amino(acetamido)quinoline scaffold: Synthesis, antiproliferative activities against melanoma cell lines, kinase inhibition, and in silico studies', European Journal of Medicinal Chemistry, vol. 70, pp. 10-21. https://doi.org/10.1016/j.ejmech.2013.06.060

New diarylamides and diarylureas possessing 8-amino(acetamido)quinoline scaffold: Synthesis, antiproliferative activities against melanoma cell lines, kinase inhibition, and in silico studies. / Koh, Eun Jeong; El-Gamal, Mohammed I.; Oh, Chang Hyun et al.
In: European Journal of Medicinal Chemistry, Vol. 70, 2013, p. 10-21.

Research output: Contribution to journal › Article › peer-review

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

SN - 0223-5234

VL - 70

SP - 10

EP - 21

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

ER -

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

Abstract

Bibliographical note

Keywords

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