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Anti-melanogenic effect of (Z)-5-(2,4-dihydroxybenzylidene) thiazolidine-2,4-dione, a novel tyrosinase inhibitor

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Abstract

We synthesized (Z)-5-(2,4-dihydroxybenzylidene)thiazolidine-2,4-dione (MHY498) as a potential tyrosinase inhibitor. MHY498 potently inhibited mushroom tyrosinase activity (mean IC50 = 3.55 μM) in a dose-dependent manner. MHY498 was more potent than the well-known tyrosinase inhibitor, kojic acid (mean IC50 = 22.79 μM). When tested in B16F10 melanoma cells treated with α-melanocyte stimulating hormone (α-MSH), MHY498 inhibited murine tyrosinase activity and decreased melanin production without inducing cytotoxicity. Docking models showed that the binding affinity of MHY498 to tyrosinase was higher than that of kojic acid, and docking simulation results indicated that the tyrosinase binding moieties of MHY498 and kojic acid were similar. Western blotting showed that tyrosinase inhibition by MHY498 partly resulted from the expressional modulations of tyrosinase and its transcription factor, microphthalmia-associated transcription factor, via the cAMP–PKA–CREB pathway. These findings suggest that MHY498 could be useful as an antimelanogenic agent for the prevention and treatment of diseases associated with skin pigmentation.

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Acknowledgments

This work was supported by the Korean National Research Foundation (NRF) funded by the Korean government (MEST) (Grant no. 2009-0083538). We thank the Aging Tissue Bank for providing us with research materials.

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Authors and Affiliations

  1. College of Pharmacy, Pusan National University, Kumjeong-gu, Busan, 609-735, Republic of Korea

    So Hee Kim, Kyoung Mi Moon, Yeon Ja Choi, Ki Wung Chung & Hae Young Chung

  2. Department of Chemistry, Dong-A University, Hadan2-dong, Saha-gu, Busan, 604-714, Republic of Korea

    Young Mi Ha

  3. Molecular Inflammation Research Centre for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Kumjeong-gu, Busan, 609-735, Republic of Korea

    Kyoung Mi Moon, Yeon Ja Choi, Hyoung Oh Jeong, Ki Wung Chung & Hae Young Chung

  4. Laboratory of Medicinal Chemistry, College of Pharmacy, Pusan National University, Kumjeong-gu, Busan, 609-735, Republic of Korea

    Yun Jung Park, Hye Jin Lee & Hyung Ryong Moon

  5. College of Pharmacy, Inje University, Gimhae, Gyeongnam, 621-749, Republic of Korea

    Pusoon Chun

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  1. So Hee Kim
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Correspondence to Hyung Ryong Moon or Hae Young Chung.

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Kim, S.H., Ha, Y.M., Moon, K.M. et al. Anti-melanogenic effect of (Z)-5-(2,4-dihydroxybenzylidene) thiazolidine-2,4-dione, a novel tyrosinase inhibitor. Arch. Pharm. Res. 36, 1189–1197 (2013). https://doi.org/10.1007/s12272-013-0184-5

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