PUBLICATION
Potent anti-melanogenic activity and favorable toxicity profile of selected 4-phenyl hydroxycoumarins in the zebrafish model and the computational molecular modeling studies
- Authors
- Veselinović, J.B., Veselinović, A.M., Ilic-Tomic, T., Davis, R., O'Connor, K., Pavic, A., Nikodinovic-Runic, J.
- ID
- ZDB-PUB-171019-11
- Date
- 2017
- Source
- Bioorganic & Medicinal Chemistry 25(24): 6286-6296 (Journal)
- Registered Authors
- Keywords
- 4-Phenyl hydroxycoumarins, Melanogenesis, Molecular docking, Tyrosinase inhibitors, Zebrafish
- MeSH Terms
-
- Animals
- Coumarins/chemistry
- Coumarins/pharmacology*
- Dose-Response Relationship, Drug
- Enzyme Inhibitors/chemistry
- Enzyme Inhibitors/pharmacology*
- Melanocytes
- Models, Animal*
- Models, Molecular
- Molecular Structure
- Monophenol Monooxygenase/antagonists & inhibitors
- Monophenol Monooxygenase/metabolism
- Structure-Activity Relationship
- Zebrafish
- PubMed
- 29042224 Full text @ Bioorg. Med. Chem.
Citation
Veselinović, J.B., Veselinović, A.M., Ilic-Tomic, T., Davis, R., O'Connor, K., Pavic, A., Nikodinovic-Runic, J. (2017) Potent anti-melanogenic activity and favorable toxicity profile of selected 4-phenyl hydroxycoumarins in the zebrafish model and the computational molecular modeling studies. Bioorganic & Medicinal Chemistry. 25(24):6286-6296.
Abstract
7-Hydroxy-4-phenylcoumarin (7C) and 5,7-dihydroxy-4-phenylcoumarin (5,7C) have been evaluated as potential anti-melanogenic agents in the zebrafish (Danio rerio) model in comparison to commercially utilized depigmenting agents hydroquinone and kojic acid. 7C and 5,7C decreased the body pigmentation at 5µg/mL, while did not affect the embryos development and survival at doses ≤50µg/mL and ≤25µg/mL. Unlike hydroquinone and kojic acid, 4-phenyl hydroxycoumarins were no melanocytotoxic, showed no cardiotoxic side effects, neither caused neutropenia in zebrafish embryos, suggesting these compounds may present novel skin-whitening agents with improved pharmacological properties. Inhibition of tyrosinase was identified as the possible mode of anti-melanogenic action. Molecular docking studies using the homology model of human tyrosinase as well as adenylate cyclase revealed excellent correlation with experimentally obtained results.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping