The natural-based optimization of kojic acid conjugated to different thio-quinazolinones as potential anti-melanogenesis agents with tyrosinase inhibitory activity.
Bioorg Med Chem
; 36: 116044, 2021 04 15.
Article
en En
| MEDLINE
| ID: mdl-33640246
ABSTRACT
Melanin pigment and melanogenesis are a two-edged sword. Melanin has a radioprotection role while melanogenesis has undesirable effects. Targeting the melanogenesis pathway, a series of kojyl thioether conjugated to different quinazolinone derivatives were designed, synthesized, and evaluated for their inhibitory activity against mushroom tyrosinase. All the synthesized compounds were screened for their anti-tyrosinase activity and all derivatives displayed better potency than kojic acid as the positive control. In this regard, 5j and 5h as the most active compounds showed an IC50 value of 0.46 and 0.50 µM, respectively. In kinetic evaluation against tyrosinase, 5j depicted an uncompetitive inhibition pattern. Designed compounds also exhibited mild antioxidant capacity. Moreover, 5j and 5h achieved good potency against the B16F10 cell line to reduce the melanin content, whilst showing limited toxicity against malignant cells. The proposed binding mode of new inhibitors evaluated through molecular docking was consistent with the results of structure-activity relationship analysis.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Pironas
/
Compuestos de Sulfhidrilo
/
Productos Biológicos
/
Monofenol Monooxigenasa
/
Inhibidores Enzimáticos
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Quinazolinonas
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Antineoplásicos
Límite:
Animals
Idioma:
En
Revista:
Bioorg Med Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Irán