Biocatalytic synthesis of acylated derivatives of troxerutin: their bioavailability and antioxidant properties in vitro

Abstract

BackgroundFlavonoid glycosides have many beneficial effects on health, but these bioactivities tend to decrease after oral administration owing to their poor lipophilicity. In this study, a facile whole-cell-based method was developed for selective preparation of monoester or diester of troxerutin, a flavonoid derivative. In addition, the bioavailabilities and antioxidant properties of troxerutin and its acylated derivatives were also investigated in cells.ResultsPseudomonas aeruginosa and Pseudomonas stutzeri cells showed high catalytic efficiency (substrate conversion > 90%) and different preferences for troxerutin, resulting in the production of its monoester (TME) and diester (TDE), respectively. The logP values of troxerutin, TME, and TDE were − 2.04 ± 0.10, − 0.75 ± 0.08, and 1.51 ± 0.05 and their Papp values were 0.34 × 10−6 ± 0.05, 0.99 × 10−6 ± 0.12, and 1.54 × 10−6 ± 0.17 cm/s, respectively. The results of hydroxyl radical, ABTS, and ORAC assays indicated that the antiradical activities of acylated derivatives did not exceed that of troxerutin, but showed higher inhibition effects upon 2,2′-azobis(2-amidinopropane) dihydrochloride-induced erythrocyte hemolysis than that of troxerutin (P < 0.05).ConclusionA facile and efficient whole-cell biocatalysis method was developed to synthesize troxerutin-acylated derivatives, markedly enhancing the bioavailability and antioxidant activities of troxerutin in cells. Additionally, the mechanism underlying the observed difference in the antioxidant activities of troxerutin and its esters was ascribed to both their free radical scavenging abilities and distribution on the cell membrane surface. Electronic supplementary materialThe online version of this article (10.1186/s12934-018-0976-x) contains supplementary material, which is available to authorized users.

Lipophilicity as a Central Component of Drug-Like Properties of Chalchones and Flavonoid Derivatives

“…Lipophilicity of a drug molecule is of particular importance due to its impact on the metabolism, pharmacokinetics, pharmacodynamics, and molecular toxicity of molecules. It correlates with the absorption, distribution, metabolism, excretion, and molecule toxicology (ADMET) processes [11,12,13,14,15,16].…”

Troxerutin flavonoid has neuroprotective properties and increases neurite outgrowth and migration of neural stem cells from the subventricular zone

“…Gallocatechin gallate and theaflavin exhibited 100% efficacy in preventing fibrils formation of Aß 42 in an extracellular chemical reaction since these molecules provide a higher number of aromatic rings and hydroxyl groups in their structures as compared to other compounds tested (Phan 2019). A number of these aromatic rings and reactive hydroxyl groups in TRX molecule [ 79 ] is comparable to that of theaflavin [ 80 ], rutin [ 81 ] and more than that of gallocatechin gallate [ 82 ] so it was assumed that the neutralizing activity of TRX against Aß 42 induced inhibition in neuronal differentiation and neurite growth in our experiments might be due to the disaggregating or antifibrillization effects of TRX. Future detailed studies are needed to prove if TRX prevents fibrillization of Aß42 in a reaction mixture.…”

Method to Improve Azo-Compound (AAPH)-Induced Hemolysis of Erythrocytes for Assessing Antioxidant Activity of Lipophilic Compounds

“…Many studies have used AAPH-induced oxidative hemolysis to measure antioxidant activity of various compounds, especially complex mixture compounds. [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] In the present study, we re-examined the methodology of AAPH-induced oxidative hemolysis and propose an improved method for evaluating antioxidant activity of various compounds, especially lipophilic compounds, using AAPH-induced hemolysis of erythrocytes.…”