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

KU-KIST Graduate School of Converging Science and Technology

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

25 Citations (Scopus)

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
Publication status	Published - 2013

Keywords

Antiproliferative activity
Diarylamide
Diarylurea
ERK kinase
Melanoma
Quinoline

ASJC Scopus subject areas

Pharmacology
Drug Discovery
Organic Chemistry

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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

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; Lee, So Ha; Sim, Taebo; Kim, Garam; Choi, Hong Seok; Hong, Jun Hee; Lee, Sang Gi; Yoo, Kyung Ho.

In: European Journal of Medicinal Chemistry, Vol. 70, 2013, p. 10-21.

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

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

Koh, Eun Jeong ; El-Gamal, Mohammed I. ; Oh, Chang Hyun ; Lee, So Ha ; Sim, Taebo ; Kim, Garam ; Choi, Hong Seok ; Hong, Jun Hee ; Lee, Sang Gi ; Yoo, Kyung Ho. / New diarylamides and diarylureas possessing 8-amino(acetamido)quinoline scaffold : Synthesis, antiproliferative activities against melanoma cell lines, kinase inhibition, and in silico studies. In: European Journal of Medicinal Chemistry. 2013 ; Vol. 70. pp. 10-21.

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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. ",

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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.

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KW - ERK kinase

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KW - Quinoline

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