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Exploring 2-mercapto-N-arylacetamide analogs as promising anti-melanogenic agents: in vitro and in vivo evaluation.
Jung, Hee Jin; Park, Hye Soo; Kim, Hye Jin; Park, Hyeon Seo; Kim, Young Eun; Jeong, Da Eun; Noh, Sang Gyun; Park, Yujin; Chun, Pusoon; Chung, Hae Young; Moon, Hyung Ryong.
Afiliação
  • Jung HJ; Department of Manufacturing Pharmacy, College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of Korea. mhr108@pusan.ac.kr.
  • Park HS; Department of Manufacturing Pharmacy, College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of Korea. mhr108@pusan.ac.kr.
  • Kim HJ; Department of Manufacturing Pharmacy, College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of Korea. mhr108@pusan.ac.kr.
  • Park HS; Department of Manufacturing Pharmacy, College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of Korea. mhr108@pusan.ac.kr.
  • Kim YE; Department of Manufacturing Pharmacy, College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of Korea. mhr108@pusan.ac.kr.
  • Jeong DE; Department of Manufacturing Pharmacy, College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of Korea. mhr108@pusan.ac.kr.
  • Noh SG; Department of Pharmacy, College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of Korea.
  • Park Y; Department of Medicinal Chemistry, New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 41061, South Korea.
  • Chun P; College of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, Gimhae, Gyeongnam 50834, Republic of Korea.
  • Chung HY; Department of Pharmacy, College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of Korea.
  • Moon HR; Department of Manufacturing Pharmacy, College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of Korea. mhr108@pusan.ac.kr.
Org Biomol Chem ; 22(37): 7671-7689, 2024 09 25.
Article em En | MEDLINE | ID: mdl-39222053
ABSTRACT
Based on the hypothesis that the 2-mercaptoacetamide moiety chelates the copper ions of tyrosinase, 2-mercapto-N-arylacetamide (2-MAA) analogs were designed and synthesized as potential tyrosinase inhibitors. Four 2-MAA analogs showed low IC50 values ranging from 0.95 to 2.0 µM against mushroom tyrosinase, which was 12-26 times lower than that of kojic acid (IC50 value = 24.3 µM). However, according to a copper ion chelation experiment performed, the 2-MAA analogs did not participate in chelation with copper ions. To identify the mode of inhibition of the 2-MAA analogs, kinetic studies were performed, and the results were supported by docking results. In addition, docking simulation results suggested that the 2-MAA analogs strongly inhibited tyrosinase activity because of the hydrogen bonding of the amide NH group and the hydrophobic interaction of the aryl ring instead of chelation with copper ions. In experiments using B16F10 cells, 2-MAA analogs were shown to inhibit melanin production by inhibiting cellular tyrosinase activity. Western blotting showed that in addition to directly inhibiting tyrosinase activity, analog 7 also has an anti-melanogenic effect by inhibiting the expression of microphthalmia-associated transcription factor (MITF) and tyrosinase. The 2-MAA analogs showed no appreciable cytotoxicity against HaCaT and B16F10 cells, making them suitable for dermal applications. In a depigmentation experiment using zebrafish embryos, analogs 1 and 2 showed more potent depigmentation effects than kojic acid even at 1000 times lower concentration than that of kojic acid. These results suggest that the 2-MAA analogs are promising anti-melanogenic agents that can inhibit most tyrosinases in various species.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Peixe-Zebra / Monofenol Mono-Oxigenase / Inibidores Enzimáticos / Acetamidas / Melaninas Limite: Animals / Humans Idioma: En Revista: Org Biomol Chem Assunto da revista: BIOQUIMICA / QUIMICA Ano de publicação: 2024 Tipo de documento: Article País de publicação: Reino Unido
Texto completo
Adicionar na Minha BVS
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XML
PubMed Links
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Peixe-Zebra / Monofenol Mono-Oxigenase / Inibidores Enzimáticos / Acetamidas / Melaninas Limite: Animals / Humans Idioma: En Revista: Org Biomol Chem Assunto da revista: BIOQUIMICA / QUIMICA Ano de publicação: 2024 Tipo de documento: Article País de publicação: Reino Unido