The Guanidine Pseudoalkaloids 10-Methoxy-Leonurine and Leonurine Act as Competitive Inhibitors of Tyrosinase

Abstract

Tyrosinase plays a key role in the production of melanin. A variety of industrial fields have shown interest in the development of tyrosinase inhibitors from plants. In this study, compounds 1–5 derived from Leonurus japonicas were evaluated to determine their ability to inhibit tyrosinase. Of these, 10-methoxy-leonurine (1) and leonurine (2) exhibited IC50 values of 7.4 ± 0.4 and 12.4 ± 0.8 μM, respectively, and acted as competitive inhibitors of tyrosinase, with Ki values in the micromolar range. In silico modeling revealed a guanidine group located in the inner cavity and a benzene ring docked within the active site of these compounds. These guanidine pseudoalkaloids show potential not only as tyrosinase inhibitors but also as lead compounds in new scaffolds for the development of novel inhibitors.

Considerations about the Continuous Assay Methods, Spectrophotometric and Spectrofluorometric, of the Monophenolase Activity of Tyrosinase

“…On the other hand, the IC50 value described is 14.64 µM and the K I value = 67.60 µM [ 10 ], but in the case of a competitive inhibitor, it can be shown that IC50 > K I , specifically IC50 = (n+1)K I , where n is the ratio of substrate concentration to Km [ 36 ]. This relationship between IC50 and K I is well established in the data shown in Tables 1 and 2 in [ 37 ] and in Table 1 in [ 38 ]. The relationship of rates of consumption of M, O 2 and formation of DC described in Table S5 of the Supporting Information [ 10 ] shows in the monophenolase activity the equality of rates of consumption of O 2 and consumption of M, however the DC formation rate is not comparative; this aspect confirms the validity of the measure measuring O 2 consumption that was described previously [ 9 ].…”

“…On the other hand, the IC50 value described is 14.64 µM and the K I value = 67.60 µM [ 10 ], but in the case of a competitive inhibitor, it can be shown that IC50 > K I , specifically IC50 = (n+1)K I , where n is the ratio of substrate concentration to Km [ 36 ]. This relationship between IC50 and K I is well established in the data shown in Tables 1 and 2 in [ 37 ] and in Table 1 in [ 38 ].…”

“…where n is the ratio of substrate concentration to Km [36]. This relationship between IC50 and K I is well established in the data shown in Tables 1 and 2 in [37] and in Table 1 in [38].…”

Phytochemical Profile and Biological Activities of Crude and Purified Leonurus cardiaca Extracts

“…Different classes of secondary metabolites have been identified in L. cardiaca . In particular, flavonoids (e.g., flavonols such as quercetin and rutin, flavones such as genkwanin and apigenin, and their relative glycosides) [ 7 ], phenylethanoid glycosides (e.g., verbascoside and lavandulifolioside) [ 8 ], iridoids (e.g., harpagide), labdane diterpenes (e.g., forskolin) [ 9 , 10 ], p -hydroxycinnamic acid derivatives (e.g., ferulic, chlorogenic and caffeic acids) [ 11 ], guanidine pseudoalkaloids (e.g., leonurine) [ 12 ], and betains (e.g., stachydrine, and turicin) [ 10 ]. The essential oil obtained from the leaves was reported to contain β -caryophyllene and α -humulene as the major compounds.…”

ANTIAGE-DB: A Database and Server for the Prediction of Anti-Aging Compounds Targeting Elastase, Hyaluronidase, and Tyrosinase

“…The binding of caffeine to Tyr promoted a conformational change of a loop so as to fit in Tyr’s active site. Two pseudoalkaloids isolated from the herb Leonurus japonicas (Yi Mu Cao) [ 180 ] (10-methoxy-leonurine and leonurine) interacted with Tyr’s active site, according to docking simulations. 10-methoxy-leonurine was totally fitted into Tyr’s active site through hydrophobic bonds between the aromatic ring and the amino acids, while the ketonic ester moiety interacted with His244 at a distance of 3.5 Å.…”