Effect of chrysin omega-3 and 6 fatty acid esters on mushroom tyrosinase activity, stability, and structure

The estreification of chrysin with α-Linolenic acid (complex I) and linoleic acid (complex II) poly unsaturated fatty acids resulted to design of new mushroom tyrosinase (MT) inhibitors. Thermodynamic parameters of enzymes, including the melting point (T_m ) and ∆G values, were obtained from thermal and chemical denaturation curves. Complexes I and II showed a competitive inhibitory effect on MT with K_i values of 0.45 and 0.29 mM, respectively. The T_m values were calculated as 328.6, 322.4, and 318 K and the ∆G values as 62.8, 52.9, and 47.1 KJ mol^-1 for the enzyme alone and its interaction with complexes I and II, respectively. Intrinsic and extrinsic fluorescence techniques showed structural instability of the enzyme in concomitance with a decrease in the regular secondary structure acquired using CD spectrometry. This data clearly prove that the new derivatives show a stronger inhibitory effect than the separate compounds. Molecular docking analysis showed that the best possible interaction condition was achieved for chrysin with n-6. PRACTICAL APPLICATIONS: MT is a suitable model in medicine for the investigation of melanogenesis, skin disorders, and hyperpigmentation because of its accessibility and close structural similarity to mammalian tyrosinase. In recent years, the designing of tyrosinase inhibitors from natural substances for prevention of hyperpigmentation in medicine, skin cosmetics, and undesired browning in agriculture and food industry has risen sharply. Many of the pharmaceutical products based on the use of flavonoids and poly unsaturated acids as natural compounds or on their semi-synthetic derivatives have been interested for investigations because of their usefulness in many pathological conditions such as inflammation, cancer, and skin disorders. The limitation of the flavonoids applications are low bioavailability, permeability, and solubility for the cells. In this study, conjugation of chrysin with n-3 and n-6 fatty acids resulted in a stronger inhibitors of MT with a synergic inhibitory effect on its activity.