(Z)-2-(Benzo[d]thiazol-2-ylamino)-5-(substituted benzylidene)thiazol-4(5H)-one Derivatives as Novel Tyrosinase Inhibitors.

Abstract

Inhibiting tyrosinase is an important goal to prevent melanin accumulation in skin and thereby to inhibit pigmentation disorders. Therefore, tyrosinase inhibitors are an attractive target in cosmetics and treatments for pigmentation disorders. However, only a few tyrosinase inhibitors are currently available because of their toxic effects to skin or lack of selectivity and stability. Here, we newly synthesized thirteen (Z)-2-(benzo[d]thiazol-2-ylamino)-5-(substituted benzylidene)thiazol-4(5H)-one derivatives and examined their effect on melanogenesis. Of these compounds, MHY2081 had the strongest inhibitory effect on tyrosinase without cytotoxicity in B16F10 melanoma cells. Consistently, melanogenesis was notably decreased by MHY2081 treatment. As an underlying mechanism, docking simulation showed that compared to kojic acid, a well-known competitive tyrosinase inhibitor which forms a hydrogen bond and aromatic interaction with tyrosinase, MHY2081 has stronger affinity with tyrosinase by forming three hydrogen bonds and a hydrophobic interaction with residues of tyrosinase. In parallel with this, Lineweaver-Burk plot analysis showed that MHY2081 is a strong competitive inhibitor of tyrosinase. In conclusion, MHY2081 may be a novel tyrosinase inhibitor for prevention and treatment of pigmentation disorders.

• Authors: Kyeong Ha Kang, Bonggi Lee, Sujin Son, Hwi Young Yun, Kyoung Mi Moon, Hyoung Oh Jeong, Dae Hyun Kim, Eun Kyeong Lee, Yeon Ja Choi, Do Hyun Kim, Pusoon Chun, Hyung Ryong Moon, Hae Young Chung
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 38 Issue 8 Pg. 1227-33 ( 2015) ISSN: 1347-5215 [Electronic] Japan
• PMID: 26235587 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzylidene Compounds
• Enzyme Inhibitors
• Melanins
• Thiazoles
• Monophenol Monooxygenase

Topics

• Animals
• Benzylidene Compounds (chemical synthesis, pharmacology)
• Cell Line
• Enzyme Inhibitors (chemical synthesis, pharmacology)
• Melanins (biosynthesis)
• Melanoma, Experimental
• Mice
• Molecular Docking Simulation
• Monophenol Monooxygenase (antagonists & inhibitors)
• Pigmentation Disorders (drug therapy, metabolism)
• Skin (enzymology, metabolism)
• Skin Pigmentation (drug effects)
• Thiazoles (chemical synthesis, pharmacology)