Melanogenic inhibitory effects of Triangularin in B16F0 melanoma cells, in vitro and molecular docking studies

Abstract

The lack of secure therapies for hyperpigmentation disorders, without serious adverse effects, and the latest reports relating melanogenic disorders with development of neurodegenerative diseases, encourage the continuing search for new drugs for the treatment of such disorders. In this sense, the plant kingdom is an important source of bioactive natural products with great potential for the research and development of new therapeutics. The present study evaluated the anti-melanogenic activity of the natural methoxylated chalcone, 2',6'-dihydroxy-4'methoxy-3'-methylchalcone (Triangularin, T), on diphenolase activity from mushroom tyrosinase and on murine B16F0 melanoma cell model. In addition, molecular modelling studies were carried out in order to understand the inhibitory activity observed. T showed a potent anti-melanogenic activity being more active than kojic acid (KA) on tyrosinase isolated of both sources and on intracellular tyrosinase. Molecular docking studies displayed important interactions between T and the active site of tyrosinase. Our results suggest that T may be useful for the treatment of hyperpigmentary disorders.

Ishophloroglucin A Isolated from Ishige okamurae Suppresses Melanogenesis Induced by α-MSH: In Vitro and In Vivo

“…In addition, tyrosinase has been demonstrated to be essential for melanogenesis [ 29 ]. Previous studies have shown that molecular docking can be used to evaluate tyrosinase inhibitory activity [ 30 , 31 ]. Thus, molecular docking calculations were performed to understand the binding model of IPA and DPHC, a known polyphenol isolated from IO, which has revealed a higher binding energy in anti-melanogenesis activity than arbutin, as a positive control.…”

The Challenging Melanoma Landscape: From Early Drug Discovery to Clinical Approval

“…Additionally, new pyrimidine-pyrrole derivatives with substituted 1,2,3-triazole nucleus, displaying IC 50 values around 13 µM against B16-F10 melanoma cells, were found to bind EGFR tyrosine kinase (through the interaction with Cys797 and other residues), as suggested by in silico docking assays [59]. Moreover, cinnamic acid derivatives and Triangularin showed in vitro antimelanogenic activity, probably due to interaction with the catalytic site of mushroom tyrosinase, through hydrogen bonds with Arg 268 and His 85, respectively [60,61].…”

Tyrosinase-Targeting Gallacetophenone Inhibits Melanogenesis in Melanocytes and Human Skin- Equivalents

“…Melanins include eumelanin (brown/black) and pheomelanin (yellow/red) and are produced from L-tyrosine. The initial step of melanin synthesis involves hydroxylation of L-tyrosine to dihydroxyphenylalanine (DOPA), and subsequently oxidation of DOPA to DOPA-quinone by tyrosinase [16][17][18][19][20], with DOPA-quinone eventually being oxidized to dopachrome. Tyrosinase catalyzes dopachrome to 5,6-dihydroxyindole (DHI).…”

“…Unfortunately, these inhibitors have undesirable side effects, owing to which the demand for alternative anti-melanogenic compounds has been increasing. Hydroquinone, which is one of the best-known clinical depigmentation agents, is known to cause erythema, stinging, irritation, and allergic contact dermatitis [16]. Even kojic acid (KA), which is an ingredient commonly used in cosmetic products, has several side effects, causing genotoxic, hepatocarcinogenic, and allergic dermatitis [16,27].…”