Furan inhibitory activity against tyrosinase and impact on B16F10 cell toxicity

• Published in: International journal of biological macromolecules 2019-09, Vol.136, p.1034-1041
• Main Authors: Barros, Marcela Rodrigues, Menezes, Thaís Meira, da Silva, Lucas Pereira, Pires, Dartagnam Sá, Princival, Jefferson Luiz, Seabra, Gustavo, Neves, Jorge Luiz
• Format: Article
• Language: English
• Subjects: Agaricales - enzymology; Animals; Antineoplastic Agents - metabolism; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Cell Survival - drug effects; Enzyme Inhibitors - metabolism; Enzyme Inhibitors - pharmacology; Furan; Furans - metabolism; Furans - pharmacology; Humans; Inhibition; Melanoma; Melanoma - pathology; Mice; Molecular Docking Simulation; Monophenol Monooxygenase - antagonists & inhibitors; Monophenol Monooxygenase - chemistry; Monophenol Monooxygenase - metabolism; Protein Conformation; Spectroscopy; Tyrosinase
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2019.06.120

Many skin disorders and diseases are related to tyrosinase activity, in particular, due to the vital role played by this enzyme in the melanogenic process. Although numerous natural and synthetic tyrosinase inhibitors have been published, substantial efforts have been made to understand the influence of tyrosinase inhibition on the viability of melanoma cells. Here, we assess the impact of two keto-derivatives: 2-acetyl-furan (F1), furfural-acetone (F2), and two carboxyl-derivatives: 2-furan-acrylic acid (F3), 5-methyl-2-furan-acrylic acid (F4), on the mushroom tyrosinase (mTYR) activity, by applying spectroscopic, kinetic and theoretical techniques. From an exploratory and theoretical point of view, results indicated that albeit all furans bind tightly to and inhibit mTYR very efficient, carboxyl-furan derivatives presented best inhibitory activities than keto- derivatives and performed the inhibition competitively and reversible. Moreover, we examined the influence of carboxyl derivative on the viability of melanoma cells. Results expose differential toxicity of these furan derivatives, which indicates a piece of evidence that furan inhibition activity may be related to its toxicity against B16F10 cells.