Identification of a potent and noncytotoxic inhibitor of melanin production

Soonho Hwang; Sang Yoon Choi; Jin Hee Lee; Shinae Kim; Jinkyung In; Sang Keun Ha; Eunjung Lee; Tae Yoon Kim; Sun Yeou Kim; Sun Choi; Sanghee Kim

doi:10.1016/j.bmc.2010.06.034

Identification of a potent and noncytotoxic inhibitor of melanin production

Soonho Hwang, Sang Yoon Choi, Jin Hee Lee, Shinae Kim, Jinkyung In, Sang Keun Ha, Eunjung Lee, Tae Yoon Kim, Sun Yeou Kim, Sun Choi, Sanghee Kim

Pharmaceutical Sciences

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

23 Scopus citations

Abstract

On the basis of a hit from random screening, biaryl amide derivatives were prepared in a combinatorial manner via parallel solution-phase synthesis, and their effects on melanocytes were investigated to discover new effective skin depigmenting agents. Among the 120 derivatives prepared, five members exhibited a >30% reduction of melanin production at 30 μM with a cell viability of >90%. In particular, compound A₃/B₅ exhibited effective inhibitory activity on melanin synthesis. Although the inhibition percentage of A₃/B₅ was slightly lower than that of the positive reference compound, phenylthiourea (PTU), A₃/B₅ demonstrated a much better cell viability than PTU. In vivo evaluation of A ₃/B₅ also showed a significant decrease of melanin pigments. In addition, the in silico classification model was built based on the experimental data of library members. Our results suggest that these biaryl amide derivatives may act as potent skin depigmenting agents.

Original language	English
Pages (from-to)	5602-5609
Number of pages	8
Journal	Bioorganic and Medicinal Chemistry
Volume	18
Issue number	15
DOIs	https://doi.org/10.1016/j.bmc.2010.06.034
State	Published - 1 Aug 2010

Keywords

Biaryl amide library
Combinatorial chemistry
Depigmenting agents
Laplacian-modified naïve Bayesian
Structure-activity relationships

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title = "Identification of a potent and noncytotoxic inhibitor of melanin production",

abstract = "On the basis of a hit from random screening, biaryl amide derivatives were prepared in a combinatorial manner via parallel solution-phase synthesis, and their effects on melanocytes were investigated to discover new effective skin depigmenting agents. Among the 120 derivatives prepared, five members exhibited a >30% reduction of melanin production at 30 μM with a cell viability of >90%. In particular, compound A3/B5 exhibited effective inhibitory activity on melanin synthesis. Although the inhibition percentage of A3/B5 was slightly lower than that of the positive reference compound, phenylthiourea (PTU), A3/B5 demonstrated a much better cell viability than PTU. In vivo evaluation of A 3/B5 also showed a significant decrease of melanin pigments. In addition, the in silico classification model was built based on the experimental data of library members. Our results suggest that these biaryl amide derivatives may act as potent skin depigmenting agents.",

keywords = "Biaryl amide library, Combinatorial chemistry, Depigmenting agents, Laplacian-modified na{\"i}ve Bayesian, Structure-activity relationships",

author = "Soonho Hwang and Choi, {Sang Yoon} and Lee, {Jin Hee} and Shinae Kim and Jinkyung In and Ha, {Sang Keun} and Eunjung Lee and Kim, {Tae Yoon} and Kim, {Sun Yeou} and Sun Choi and Sanghee Kim",

note = "Funding Information: This work was supported by the WCU program ( R32-2008-000-10098-0 ) through KOSEF funded by MEST and the NCRC program ( R15-2006-020 ) of the MEST and NRF through the Center for Cell Signaling & Drug Discovery Research at Ewha Womans University. ",

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AU - Hwang, Soonho

AU - Choi, Sang Yoon

AU - Lee, Jin Hee

AU - Kim, Shinae

AU - In, Jinkyung

AU - Ha, Sang Keun

AU - Lee, Eunjung

AU - Kim, Tae Yoon

AU - Kim, Sun Yeou

AU - Choi, Sun

AU - Kim, Sanghee

N1 - Funding Information: This work was supported by the WCU program ( R32-2008-000-10098-0 ) through KOSEF funded by MEST and the NCRC program ( R15-2006-020 ) of the MEST and NRF through the Center for Cell Signaling & Drug Discovery Research at Ewha Womans University.

PY - 2010/8/1

Y1 - 2010/8/1

N2 - On the basis of a hit from random screening, biaryl amide derivatives were prepared in a combinatorial manner via parallel solution-phase synthesis, and their effects on melanocytes were investigated to discover new effective skin depigmenting agents. Among the 120 derivatives prepared, five members exhibited a >30% reduction of melanin production at 30 μM with a cell viability of >90%. In particular, compound A3/B5 exhibited effective inhibitory activity on melanin synthesis. Although the inhibition percentage of A3/B5 was slightly lower than that of the positive reference compound, phenylthiourea (PTU), A3/B5 demonstrated a much better cell viability than PTU. In vivo evaluation of A 3/B5 also showed a significant decrease of melanin pigments. In addition, the in silico classification model was built based on the experimental data of library members. Our results suggest that these biaryl amide derivatives may act as potent skin depigmenting agents.

AB - On the basis of a hit from random screening, biaryl amide derivatives were prepared in a combinatorial manner via parallel solution-phase synthesis, and their effects on melanocytes were investigated to discover new effective skin depigmenting agents. Among the 120 derivatives prepared, five members exhibited a >30% reduction of melanin production at 30 μM with a cell viability of >90%. In particular, compound A3/B5 exhibited effective inhibitory activity on melanin synthesis. Although the inhibition percentage of A3/B5 was slightly lower than that of the positive reference compound, phenylthiourea (PTU), A3/B5 demonstrated a much better cell viability than PTU. In vivo evaluation of A 3/B5 also showed a significant decrease of melanin pigments. In addition, the in silico classification model was built based on the experimental data of library members. Our results suggest that these biaryl amide derivatives may act as potent skin depigmenting agents.

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KW - Depigmenting agents

KW - Laplacian-modified naïve Bayesian

KW - Structure-activity relationships

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Identification of a potent and noncytotoxic inhibitor of melanin production

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Keywords

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