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Synthesis and evaluation of 3-hydroxyquinolin-2(1H)-one derivatives as inhibitors of tyrosinase.
Jacobs, Maria E; Petzer, Jacobus P; Pretorius, Judey; Cloete, Stephanus J; Crous, Chantalle; Petzer, Anél.
Afiliación
  • Jacobs ME; Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom 2520, South Africa. Electronic address: maria.elizabethj2000@gmail.com.
  • Petzer JP; Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom 2520, South Africa; Pharmaceutical Chemistry, School of Pharmacy, North-West University, Potchefstroom 2520, South Africa. Electronic address: jacques.petzer@nwu.ac.za.
  • Pretorius J; Biomedical Emporium, Pretoria, South Africa. Electronic address: drjudey@biomedicalemporium.com.
  • Cloete SJ; Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom 2520, South Africa. Electronic address: 23496959@mynwu.ac.za.
  • Crous C; Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom 2520, South Africa. Electronic address: 21204756@mynwu.ac.za.
  • Petzer A; Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom 2520, South Africa; Pharmaceutical Chemistry, School of Pharmacy, North-West University, Potchefstroom 2520, South Africa. Electronic address: anel.petzer@nwu.ac.za.
Bioorg Med Chem Lett ; 109: 129823, 2024 Sep 01.
Article en En | MEDLINE | ID: mdl-38823727
ABSTRACT
The tyrosinase (TYR) enzyme catalyses sequential reactions in the melanogenesis pathway l-tyrosine is oxidised to yield L-3,4-dihydroxyphenylalanine (l-dopa), which in turn is converted to dopaquinone. These two reactions are the first two steps of melanin biosynthesis and are rate limiting. The accumulation or overproduction of melanin may cause skin hyperpigmentation and inhibitors of TYR are thus of interest to the cosmeceutical industry. Several TYR inhibitors are used to treat skin hyperpigmentation, however, some are ineffective and possess questionable safety profiles. This emphasises the need to develop novel TYR inhibitors with better safety and efficacy profiles. The small molecule, 3-hydroxycoumarin, has been reported to be a good potency TYR inhibitor (IC50 = 2.49 µM), and based on this, a series of eight structurally related 3-hydroxyquinolin-2(1H)-one derivatives were synthesised with the aim to discover novel TYR inhibitors. The results showed that four of the derivatives inhibited TYR from the champignon mushroom Agaricus bisporus (abTYR) with IC50 < 6.11 µM. The most potent inhibitor displayed an IC50 value of 2.52 µM. Under the same conditions, the reference inhibitors, thiamidol and kojic acid, inhibited abTYR with IC50 values of 0.130 and 26.4 µM, respectively. Based on the small molecular structures of the active 3-hydroxyquinolin-2(1H)-one inhibitors which are amenable to structure optimisation, it may be concluded that this class of compounds are good leads for the design of TYR inhibitors for cosmeceutical applications.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Monofenol Monooxigenasa / Inhibidores Enzimáticos Idioma: En Revista: Bioorg Med Chem Lett Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2024 Tipo del documento: Article

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Monofenol Monooxigenasa / Inhibidores Enzimáticos Idioma: En Revista: Bioorg Med Chem Lett Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2024 Tipo del documento: Article