Novel Anti-Melanogenic Compounds, (<i>Z</i>)-5-(Substituted Benzylidene)-4-thioxothiazolidin-2-one Derivatives: In Vitro and In Silico Insights
To confirm that the β-phenyl-α,β-unsaturated thiocarbonyl (PUSTC) scaffold, similar to the β-phenyl-α,β-unsaturated carbonyl (PUSC) scaffold, acts as a core inhibitory structure for tyrosinase, twelve (<i>Z</i>)-5-(substituted benzylidene)-4-thioxothiazolidin-2-one ((<i>Z</i>...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/16/4963 |
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| author | Heejeong Choi Il Young Ryu Inkyu Choi Sultan Ullah Hee Jin Jung Yujin Park Yeongmu Jeong YeJi Hwang Sojeong Hong In-Soo Yoon Hwayoung Yun Min-Soo Kim Jin-Wook Yoo Yunjin Jung Pusoon Chun Hyung Ryong Moon |
| author_facet | Heejeong Choi Il Young Ryu Inkyu Choi Sultan Ullah Hee Jin Jung Yujin Park Yeongmu Jeong YeJi Hwang Sojeong Hong In-Soo Yoon Hwayoung Yun Min-Soo Kim Jin-Wook Yoo Yunjin Jung Pusoon Chun Hyung Ryong Moon |
| author_sort | Heejeong Choi |
| collection | DOAJ |
| description | To confirm that the β-phenyl-α,β-unsaturated thiocarbonyl (PUSTC) scaffold, similar to the β-phenyl-α,β-unsaturated carbonyl (PUSC) scaffold, acts as a core inhibitory structure for tyrosinase, twelve (<i>Z</i>)-5-(substituted benzylidene)-4-thioxothiazolidin-2-one ((<i>Z</i>)-BTTZ) derivatives were designed and synthesized. Seven of the twelve derivatives showed stronger inhibitory activity than kojic acid against mushroom tyrosinase. Compound <b>2b</b> (IC<sub>50</sub> = 0.47 ± 0.97 µM) exerted a 141-fold higher inhibitory potency than kojic acid. Kinetic studies’ results confirmed that compounds <b>2b</b> and <b>2f</b> are competitive tyrosinase inhibitors, which was supported by high binding affinities with the active site of tyrosinase by docking simulation. Docking results using a human tyrosinase homology model indicated that <b>2b</b> and <b>2f</b> might potently inhibit human tyrosinase. In vitro assays of <b>2b</b> and <b>2f</b> were conducted using B16F10 melanoma cells. Compounds <b>2b</b> and <b>2f</b> significantly and concentration-dependently inhibited intracellular melanin contents, and the anti-melanogenic effects of <b>2b</b> at 10 µM and <b>2f</b> at 25 µM were considerably greater than the inhibitory effect of kojic acid at 25 µM. Compounds <b>2b</b> and <b>2f</b> similarly inhibited cellular tyrosinase activity and melanin contents, indicating that the anti-melanogenic effects of both were due to tyrosinase inhibition. A strong binding affinity with the active site of tyrosinase and potent inhibitions of mushroom tyrosinase, cellular tyrosinase activity, and melanin generation in B16F10 cells indicates the PUSTC scaffold offers an attractive platform for the development of novel tyrosinase inhibitors. |
| first_indexed | 2024-03-10T08:33:16Z |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-10T08:33:16Z |
| publishDate | 2021-08-01 |
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| series | Molecules |
| spelling | doaj.art-81fbfe9f798140849b5c9ab47083a2ed2023-11-22T08:54:33ZengMDPI AGMolecules1420-30492021-08-012616496310.3390/molecules26164963Novel Anti-Melanogenic Compounds, (<i>Z</i>)-5-(Substituted Benzylidene)-4-thioxothiazolidin-2-one Derivatives: In Vitro and In Silico InsightsHeejeong Choi0Il Young Ryu1Inkyu Choi2Sultan Ullah3Hee Jin Jung4Yujin Park5Yeongmu Jeong6YeJi Hwang7Sojeong Hong8In-Soo Yoon9Hwayoung Yun10Min-Soo Kim11Jin-Wook Yoo12Yunjin Jung13Pusoon Chun14Hyung Ryong Moon15Laboratory of Medicinal Chemistry, College of Pharmacy, Pusan National University, Busan 46241, KoreaLaboratory of Medicinal Chemistry, College of Pharmacy, Pusan National University, Busan 46241, KoreaLaboratory of Medicinal Chemistry, College of Pharmacy, Pusan National University, Busan 46241, KoreaDepartment of Molecular Medicine, The Scripps Research Institute, Jupiter, FL 33458, USALaboratory of Medicinal Chemistry, College of Pharmacy, Pusan National University, Busan 46241, KoreaLaboratory of Medicinal Chemistry, College of Pharmacy, Pusan National University, Busan 46241, KoreaLaboratory of Medicinal Chemistry, College of Pharmacy, Pusan National University, Busan 46241, KoreaLaboratory of Medicinal Chemistry, College of Pharmacy, Pusan National University, Busan 46241, KoreaLaboratory of Medicinal Chemistry, College of Pharmacy, Pusan National University, Busan 46241, KoreaLaboratory of Medicinal Chemistry, College of Pharmacy, Pusan National University, Busan 46241, KoreaLaboratory of Medicinal Chemistry, College of Pharmacy, Pusan National University, Busan 46241, KoreaLaboratory of Medicinal Chemistry, College of Pharmacy, Pusan National University, Busan 46241, KoreaLaboratory of Medicinal Chemistry, College of Pharmacy, Pusan National University, Busan 46241, KoreaLaboratory of Medicinal Chemistry, College of Pharmacy, Pusan National University, Busan 46241, KoreaCollege of Pharmacy, Inje University, Gyeongnam, Gimhae 50834, KoreaLaboratory of Medicinal Chemistry, College of Pharmacy, Pusan National University, Busan 46241, KoreaTo confirm that the β-phenyl-α,β-unsaturated thiocarbonyl (PUSTC) scaffold, similar to the β-phenyl-α,β-unsaturated carbonyl (PUSC) scaffold, acts as a core inhibitory structure for tyrosinase, twelve (<i>Z</i>)-5-(substituted benzylidene)-4-thioxothiazolidin-2-one ((<i>Z</i>)-BTTZ) derivatives were designed and synthesized. Seven of the twelve derivatives showed stronger inhibitory activity than kojic acid against mushroom tyrosinase. Compound <b>2b</b> (IC<sub>50</sub> = 0.47 ± 0.97 µM) exerted a 141-fold higher inhibitory potency than kojic acid. Kinetic studies’ results confirmed that compounds <b>2b</b> and <b>2f</b> are competitive tyrosinase inhibitors, which was supported by high binding affinities with the active site of tyrosinase by docking simulation. Docking results using a human tyrosinase homology model indicated that <b>2b</b> and <b>2f</b> might potently inhibit human tyrosinase. In vitro assays of <b>2b</b> and <b>2f</b> were conducted using B16F10 melanoma cells. Compounds <b>2b</b> and <b>2f</b> significantly and concentration-dependently inhibited intracellular melanin contents, and the anti-melanogenic effects of <b>2b</b> at 10 µM and <b>2f</b> at 25 µM were considerably greater than the inhibitory effect of kojic acid at 25 µM. Compounds <b>2b</b> and <b>2f</b> similarly inhibited cellular tyrosinase activity and melanin contents, indicating that the anti-melanogenic effects of both were due to tyrosinase inhibition. A strong binding affinity with the active site of tyrosinase and potent inhibitions of mushroom tyrosinase, cellular tyrosinase activity, and melanin generation in B16F10 cells indicates the PUSTC scaffold offers an attractive platform for the development of novel tyrosinase inhibitors.https://www.mdpi.com/1420-3049/26/16/4963tyrosinasePUSTC scaffoldanti-melanogenic effectdocking simulation |
| spellingShingle | Heejeong Choi Il Young Ryu Inkyu Choi Sultan Ullah Hee Jin Jung Yujin Park Yeongmu Jeong YeJi Hwang Sojeong Hong In-Soo Yoon Hwayoung Yun Min-Soo Kim Jin-Wook Yoo Yunjin Jung Pusoon Chun Hyung Ryong Moon Novel Anti-Melanogenic Compounds, (<i>Z</i>)-5-(Substituted Benzylidene)-4-thioxothiazolidin-2-one Derivatives: In Vitro and In Silico Insights Molecules tyrosinase PUSTC scaffold anti-melanogenic effect docking simulation |
| title | Novel Anti-Melanogenic Compounds, (<i>Z</i>)-5-(Substituted Benzylidene)-4-thioxothiazolidin-2-one Derivatives: In Vitro and In Silico Insights |
| title_full | Novel Anti-Melanogenic Compounds, (<i>Z</i>)-5-(Substituted Benzylidene)-4-thioxothiazolidin-2-one Derivatives: In Vitro and In Silico Insights |
| title_fullStr | Novel Anti-Melanogenic Compounds, (<i>Z</i>)-5-(Substituted Benzylidene)-4-thioxothiazolidin-2-one Derivatives: In Vitro and In Silico Insights |
| title_full_unstemmed | Novel Anti-Melanogenic Compounds, (<i>Z</i>)-5-(Substituted Benzylidene)-4-thioxothiazolidin-2-one Derivatives: In Vitro and In Silico Insights |
| title_short | Novel Anti-Melanogenic Compounds, (<i>Z</i>)-5-(Substituted Benzylidene)-4-thioxothiazolidin-2-one Derivatives: In Vitro and In Silico Insights |
| title_sort | novel anti melanogenic compounds i z i 5 substituted benzylidene 4 thioxothiazolidin 2 one derivatives in vitro and in silico insights |
| topic | tyrosinase PUSTC scaffold anti-melanogenic effect docking simulation |
| url | https://www.mdpi.com/1420-3049/26/16/4963 |
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