Efficient Enzymatic Synthesis of Lipophilic Phenolic Glycoside Azelaic Acid Esters and Their Depigmenting Activity

Abstract

In this paper, an enzymatic route for synthesizing phenolic glycoside azelaic acid esters was successfully set up via lipase-catalyzed esterification and transesterification. Among the lipases tested, Candida antarctica lipase B (Novozyme 435) showed the highest activity in catalyzing esterification and Thermomyces lanuginosus (Lipozyme TLIM) gave the highest substrate conversion in catalyzing transesterification for the synthesis of ester. The addition of 4A molecular sieves into the reaction system is found to be an effective method for in situ absorption of the byproduct water and methanol, with which the substrate conversions of the enzymatic esterification and transesterification were 98.7 and 95.1%, respectively. Also, the main product ratios in transesterification were above 99.0% with lipozyme TLIM as a catalyst because the hydrolysis reaction was hindered. The results of the physical and biological properties indicate that all esters had higher Clog p values than their parent compounds. Also, the esters showed higher intracellular tyrosinase inhibitory and depigmentating activities than phenolic glycosides, azelaic acid (AA), and their physical mixtures due to their higher membrane penetration and tyrosinase inhibitory effects. In particular, piceid 6″-O-azelaic acid ester (PIA) showed the strongest inhibitory effect against melanin production. Its inhibitory rate was 77.4% at a concentration of 0.25 mM, about 4.2 times higher than that of arbutin (18.5%).

Inhibition of α-glucosidase activity and intestinal glucose transport to assess the in vivo anti-hyperglycemic potential of dodecyl-acylated phlorizin and polydatin derivatives

“…7 Fortunately, a diet of natural active compounds with α-glucosidase inhibitory activity, such as anthocyanins, 8 flavonoids 9 and fatty acids, 10 has been proven to be a safe and effective way to control hyperglycemia. 11 Phlorizin (C 21 H 24 O 10 , phloretin-2′-β-D-glucopyranoside) and polydatin (C 20 H 22 O 8 , 3,4″,5-trihydroxystilbene-3-β-D-glucopyranoside) are antioxidant phenolic glycosides and have a variety of beneficial in vivo biological activities, 12 such as anti-inflammation, anti-fatigue, hepatoprotection, etc. However, only a few studies reported the in vitro inhibition activity of phlorizin against α-glucosidase.…”

“…14 The α-glucosidase inhibition mechanism and hypoglycemic activity of phlorizin and polydatin in the intestine were indeed lacking. 15 In addition, we efficiently synthesized dodecyl-acylated derivatives of phlorizin and polydatin in a previous study, 12 and acylation was shown to enhance the tyrosinase inhibitory capacity of phlorizin and isoquercitrin. 16 Thus, the acylated derivatives of phlorizin and polydatin may exhibit stronger α-glucosidase inhibitory activity.…”

“…Dodecyl acylation also enhanced the lipophilicity and intestinal permeability of phlorizin and polydatin. 12 The small intestine is one of the main organs involved in glucose uptake from the diet. 20 Therefore, the effect of dodecyl phlorizin and dodecyl polydatin on intestinal glucose uptake needs further investigation, which is closely related to the in vivo hypoglycemic activity.…”

Acylation modification enhanced encapsulation ability of baicalin by liposome, and liposome improved physicochemical properties and cytotoxicity of baicalin esters

“…Some avonoid glycoside esters have been approved as fat-soluble antioxidants for use in oils and other foods, such as propyl gallate and tea polyphenol palmitate [1]. Flavonoid glycoside esters exert excellent antioxidant effects, cellular absorption, and other biological activities than their parent compounds, such as lipid-lowering activity, antimicrobial activity, and antimelanogenic effect [2][3][4]. Therefore, avonoid glycoside esters could be used as potential functional active ingredients or additives in food, cosmetics, and nutraceuticals.…”