Synthesis and biological evaluations of oleanolic acid indole derivatives as hyaluronidase inhibitors with enhanced skin permeability.
J Enzyme Inhib Med Chem
; 36(1): 1665-1678, 2021 Dec.
Article
em En
| MEDLINE
| ID: mdl-34309457
ABSTRACT
Oleanolic acid (OA) is a natural cosmeceutical compound with various skin beneficial activities including inhibitory effect on hyaluronidase but the anti-hyaluronidase activity and mechanisms of action of its synthetic analogues remain unclear. Herein, a series of OA derivatives were synthesised and evaluated for their inhibitory effects on hyaluronidase. Compared to OA, an induction of fluorinated (6c) and chlorinated (6g) indole moieties led to enhanced anti-hyaluronidase activity (IC50 = 80.3 vs. 9.97 and 9.57 µg/mL, respectively). Furthermore, spectroscopic and computational studies revealed that 6c and 6g can bind to hyaluronidase protein and alter its secondary structure leading to reduced enzyme activity. In addition, OA indole derivatives showed feasible skin permeability in a slightly acidic environment (pH = 6.5) and 6c exerted skin protective effect by reducing cellular reactive oxygen species in human skin keratinocytes. Findings from the current study support that OA indole derivatives are potential cosmeceuticals with anti-hyaluronidase activity.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ácido Oleanólico
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Pele
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Inibidores Enzimáticos
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Hialuronoglucosaminidase
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Indóis
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article