Identification of indoline-2-thione analogs as novel potent inhibitors of α-melanocyte stimulating hormone induced melanogenesis

Pillaiyar Thanigaimalai; Ki Cheul Lee; Vinay Kumar Sharma; Niti Sharma; Eunmiri Roh; Youngsoo Kim; Sang Hun Jung

doi:10.1248/cpb.59.1285

Identification of indoline-2-thione analogs as novel potent inhibitors of α-melanocyte stimulating hormone induced melanogenesis

Pillaiyar Thanigaimalai, Ki Cheul Lee, Vinay Kumar Sharma, Niti Sharma, Eunmiri Roh, Youngsoo Kim, Sang Hun Jung

The Hormel Institute

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

8 Scopus citations

Abstract

Based on the hits, 3,4-dihydroquinazoline-2-thione (1) and benzimidazole-2-thione (2), a series of indole-2-thione (3) and indole-2-thiol inhibitors (4) of melanogenesis were designed, synthesized and evaluated in melanoma B16 cells under the stimulant of α-melanocyte stimulating hormone (α-MSH). The indole-2-thione compounds (3a-g) exhibited an effective inhibitory activity on melanin synthesis. The Structure-Activity Relationship (SAR) studies of 2 have revealed that in potent inhibitor 3a (>100% inhibition at 30μM, IC ₅₀=1.40μM) the role of nitrogen (3-N) at 3-position is insignificance. In addition, the hydrophobic substituents of 3 were better than the hydrophilic one. However, conversion of thione (-C=S, 3) to thiol (-C-SH, 4) led to decrease in the potency.

Original language	English (US)
Pages (from-to)	1285-1288
Number of pages	4
Journal	Chemical and Pharmaceutical Bulletin
Volume	59
Issue number	10
DOIs	https://doi.org/10.1248/cpb.59.1285
State	Published - Oct 2011

Keywords

Benzimidazole-2-thione
Indole-2-thiol
Inoline-2-thione
Melanogenesis inhibitor

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10.1248/cpb.59.1285

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title = "Identification of indoline-2-thione analogs as novel potent inhibitors of α-melanocyte stimulating hormone induced melanogenesis",

abstract = "Based on the hits, 3,4-dihydroquinazoline-2-thione (1) and benzimidazole-2-thione (2), a series of indole-2-thione (3) and indole-2-thiol inhibitors (4) of melanogenesis were designed, synthesized and evaluated in melanoma B16 cells under the stimulant of α-melanocyte stimulating hormone (α-MSH). The indole-2-thione compounds (3a-g) exhibited an effective inhibitory activity on melanin synthesis. The Structure-Activity Relationship (SAR) studies of 2 have revealed that in potent inhibitor 3a (>100% inhibition at 30μM, IC 50=1.40μM) the role of nitrogen (3-N) at 3-position is insignificance. In addition, the hydrophobic substituents of 3 were better than the hydrophilic one. However, conversion of thione (-C=S, 3) to thiol (-C-SH, 4) led to decrease in the potency.",

keywords = "Benzimidazole-2-thione, Indole-2-thiol, Inoline-2-thione, Melanogenesis inhibitor",

author = "Pillaiyar Thanigaimalai and Lee, {Ki Cheul} and Sharma, {Vinay Kumar} and Niti Sharma and Eunmiri Roh and Youngsoo Kim and Jung, {Sang Hun}",

year = "2011",

month = oct,

doi = "10.1248/cpb.59.1285",

language = "English (US)",

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T1 - Identification of indoline-2-thione analogs as novel potent inhibitors of α-melanocyte stimulating hormone induced melanogenesis

AU - Thanigaimalai, Pillaiyar

AU - Lee, Ki Cheul

AU - Sharma, Vinay Kumar

AU - Sharma, Niti

AU - Roh, Eunmiri

AU - Kim, Youngsoo

AU - Jung, Sang Hun

PY - 2011/10

Y1 - 2011/10

N2 - Based on the hits, 3,4-dihydroquinazoline-2-thione (1) and benzimidazole-2-thione (2), a series of indole-2-thione (3) and indole-2-thiol inhibitors (4) of melanogenesis were designed, synthesized and evaluated in melanoma B16 cells under the stimulant of α-melanocyte stimulating hormone (α-MSH). The indole-2-thione compounds (3a-g) exhibited an effective inhibitory activity on melanin synthesis. The Structure-Activity Relationship (SAR) studies of 2 have revealed that in potent inhibitor 3a (>100% inhibition at 30μM, IC 50=1.40μM) the role of nitrogen (3-N) at 3-position is insignificance. In addition, the hydrophobic substituents of 3 were better than the hydrophilic one. However, conversion of thione (-C=S, 3) to thiol (-C-SH, 4) led to decrease in the potency.

AB - Based on the hits, 3,4-dihydroquinazoline-2-thione (1) and benzimidazole-2-thione (2), a series of indole-2-thione (3) and indole-2-thiol inhibitors (4) of melanogenesis were designed, synthesized and evaluated in melanoma B16 cells under the stimulant of α-melanocyte stimulating hormone (α-MSH). The indole-2-thione compounds (3a-g) exhibited an effective inhibitory activity on melanin synthesis. The Structure-Activity Relationship (SAR) studies of 2 have revealed that in potent inhibitor 3a (>100% inhibition at 30μM, IC 50=1.40μM) the role of nitrogen (3-N) at 3-position is insignificance. In addition, the hydrophobic substituents of 3 were better than the hydrophilic one. However, conversion of thione (-C=S, 3) to thiol (-C-SH, 4) led to decrease in the potency.

KW - Benzimidazole-2-thione

KW - Indole-2-thiol

KW - Inoline-2-thione

KW - Melanogenesis inhibitor

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Identification of indoline-2-thione analogs as novel potent inhibitors of α-melanocyte stimulating hormone induced melanogenesis

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