Biocatalytic synthesis,structural elucidation,antioxidant capacity and tyrosinase inhibition activity of long chain fatty acid acylated derivatives of phloridzin and isoquercitrin

Our present investigation describes the regioselective enzymatic acylation of two series of acylated derivatives of phloridzin and isoquercitrin with six different long chain saturated, mono- and poly-unsaturated fatty acids. The biocatalytic synthesis was optimized to achieve 81–98% yields, using immobilized lipase B, from Candida antarctica (Novozym 435®), in acetone at 45 °C. The synthesized esters have been analyzed by ¹H NMR, ¹³C NMR spectroscopy and evaluated for their antioxidant capacity and tyrosinase inhibition, using in vitro assays. Among all the phloridzin and isoquercitrin derivatives, the greatest potential for inhibition of tyrosinase activity (p ?0.05) was exhibited by the α-linolenic acid ester of isoquercitrin.     

New acylated anthocyanins from purple yam and their antioxidant activity

Purple yam (Dioscorea alata L.), which is widely distributed in tropical and subtropical regions, is characterized by its color and viscosity. Previous studies have shown that purple yams contain a variety of acylated anthocyanins that exhibit higher levels of antioxidant activity than the corresponding nonacylated compounds. In this study, the pigments found in purple yams from the Philippines (D. alata) were isolated and evaluated in terms of antioxidant activity. Four new acylated anthocyanins, alanins (1–4) were isolated from the MeOH extracts of purple yam, which were subsequently determined to be cyanidin (1, 2, and 4) and peonidin (3) type compounds, along with four known anthocyanins (5–8). The structures of 1–4 were determined by spectroscopic methods, including NMR and MS analyses. The antioxidant activities of anthocyanins 1–8 were investigated using oxygen radical absorbing capacity and ferric reducing antioxidant power assays.     

Biocatalytic synthesis and antitumor activities of novel silybin acylated derivatives with dicarboxylic acids

Novel silybin acylated derivatives with dicarboxylic acids were prepared in various organic solvents using immobilized Candida antarctica lipase B (Novozym 435(?)). The reaction parameters affecting the silybin conversion, such as the nature of the organic solvent and the acyl donor used were investigated. The antiproliferative effects of silybin monoesters, and their ability to modulate the secretion of vascular endothelial growth factor (VEGF) were estimated using K562 human lymphoblastoma cells and compared to the parental compound. The synthesized esters retained the biological function of silybin and in some cases were more effective, indicating that target biotransformation may generate novel compounds with improved antitumor and antiangiogenic activities.     

Microwave-assisted synthesis and antimicrobial activities of flavonoid derivatives

Eleven flavonoid derivatives were synthesised using a modified Baker-Venkataraman rearrangement, and subsequent microwave-assisted closure of the heterocyclic ring. All of the synthetic compounds displayed antifungal activity against Aspergillus niger and Fusarium oxysporium, and two of the synthetic flavonoid analogues exhibited significant activity against methicillin-resistant Staphylococcus aureus.     

黄花倒水莲花中黄酮苷类成分的分离、鉴定及抗氧化活性研究

该研究采用硅胶、Sephadex LH-20柱色谱和HPLC进行分离纯化,并结合1D-NMR波谱数据和文献比对,研究了黄花倒水莲花中黄酮类成分及抗氧化活性。结果表明：（1）从黄花倒水莲花95%乙醇提取物的乙酸乙酯部位中分离鉴定出6个黄酮苷类化合物,即紫云英苷（1）、槲皮素-3-O-β-D-葡萄糖苷（2）、槲皮素-3-O-β-吡喃木糖苷（3）、槲皮素-3-O-α-L-吡喃阿拉伯糖苷（4）、异鼠李素-3-O-β-葡萄糖苷（5）、芦丁（6）,其中化合物1-6均为首次从该植物中分离得到。（2）分别采用DPPH·自由基清除法及FRAP法对花的不同极性部位和所获得化合物进行总抗氧化能力评价,结果显示化合物1-6均表现出较好的抗氧化作用,其中化合物4的总抗氧化能力达到（4.533±0.13）mmol·g^-1(Vc为5.951±0.25 mmol·g^-1)。该研究结果不仅丰富了黄花倒水莲花的物质基础,而且为其今后的综合开发利用提供了科学依据。     

The basic antioxidant structure for flavonoid derivatives

An antioxidant structure-activity study is carried out in this work with ten flavonoid compounds using quantum chemistry calculations with the functional of density theory method. According to the geometry obtained by using the B3LYP/6-31G(d) method, the HOMO, ionization potential, stabilization energies, and spin density distribution showed that the flavonol is the more antioxidant nucleus. The spin density contribution is determinant for the stability of the free radical. The number of resonance structures is related to the π-type electron system. 3-hydroxyflavone is the basic antioxidant structure for the simplified flavonoids studied here. The electron abstraction is more favored in the molecules where ether group and 3-hydroxyl are present, nonetheless 2,3-double bond and carbonyl moiety are facultative.     

Oxidised derivatives of silybin and their antiradical and antioxidant activity

Carboxylic acids derived from silybin (1) and 2,3-dehydrosilybin (2) with improved water solubility were prepared by selective oxidation of parent compounds and a new inexpensive method for preparation of 2,3-dehydrosilybin from silybin was developed and optimised. The antioxidative properties of the above-mentioned compounds and of side product 3a from oxidation of compound 1 were determined by cyclic voltammetry, free radical scavenging (DPPH, superoxide) assays, and by inhibition of in vitro generated liver microsomal lipid peroxidation. Dehydrogenation at C((2))-C((3)) in flavonolignans (silybin vs 2,3-dehydrosilybin; silybinic acid vs 2,3-dehydrosilybinic acid) strongly improved antioxidative properties (analogously as in flavonoids taxifolin vs quercetin). Thus, in antioxidative properties, dehydrosilybin was superior to silybin by one order, but its water solubility is too low for application in aqueous milieu. On the other hand, 2,3-dehydrosilybinic acid is a fairly soluble derivative with antilipoperoxidation and antiradical activities better than that of silybin.     

Regioselective O-deacylation of fully acylated glycosides and 1,2-O-isopropylidenealdofuranose derivatives with hydrazine hydrate

On hydrazinolysis in 1:4 acetic acid-pyridine, and in pyridine, partial O-deacylation of fully acylated methyl glycosides and some other glycosyl compounds (23 compounds) was found to be induced, to give, in good yields, products bearing one free hydroxyl group; the results obtained indicated that, among the primary and secondary O-acyl groups, the 2-O-acyl groups were, in general, the most labile toward the nucleophile (hydrazine). Hydrazinolysis of 1,2-O-isopropylidenealdofuranose acylates (3 compounds), on the other hand, gave, in high yield, the corresponding monoacyl derivatives having the protecting group on their primary hydroxyl group. The factors possibly involved in the regioselectivity of the hydrazinolysis were discussed.     

The biosynthesis of flavonoid glycosides and their importance in chemosystematics

The present article reviews flavonoid O-glycosyltransferases with respect to the historical background, isolation and purification methods, properties of the enzymes involved (especially substrate specificities) and genetic control. The possible biosynthetic pathway leading to the formation of C-glycosides is also discussed. The second part of the article is an attempt to indicate the importance of glycosylation patterns in the field of chemosystematics, especially on the intra- and infra-specific levels. The position and nature of glycosylation are first discussed, and this is followed by examples indicating the importance of glycosylation patterns.     

Use of ionic liquids as media for the biocatalytic preparation of flavonoid derivatives with antioxidant potency

Biocatalytic preparation of acylated derivatives of flavonoid glycosides was performed using various immobilized lipases in two different ionic liquids, namely 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim]BF(4)) and 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim]PF(6)). The influence of various reaction parameters on the performance and the regioselectivity of the biocatalytic process was pointed out, using as model reaction the acylation of naringin and rutin with vinyl butyrate, catalyzed by immobilized Candida antarctica lipase at 60 degrees C. The biocatalytic modification of flavonoids strongly depended on the ionic liquid used, the molar ratio of substrates, as well as the acyl donor chain length. The highest conversion yield (about 65% after 96 h of incubation) was obtained with short chain acyl donors (up to four carbon atoms), at a relatively high molar ratio (10-15) in both ionic liquids used. The amount of monoacylated flavonoid derivatives produced in a single-step biocatalytic process in [bmim]BF(4) was up to 5.5 g/L for monoacylated rutin and 30 g/L for monoacylated naringin. The regioselectivity of the process was higher in [bmim]BF(4) than in [bmim]PF(6) or organic solvents. Reaction rates observed in ionic liquids were up to four times higher than those reported for organic media. The acylation of sugar moiety of rutin with various acyl donors affected its antioxidant potential towards both isolated LDL and total serum model in vitro. A significant increase of antioxidant activity was observed for rutin-4'-O-oleate.     

Newly synthesized dopamine ester derivatives and assessment of their antioxidant,antimicrobial and hemolytic activities

Preparation of dopamine derivatives was carried out as a response to the increasing demand for new lipophilized antioxidants in food, cosmetic and pharmaceutical industries. A large series of dopamine esters (DA-C₃ to DA-C_18:1) with increasing lipophilicity was synthesized using lipase from Candida antarctica (Novozyme 435) as a biocatalyst. The highest conversion yield (52.75%) was reached when caprylic acid (DA-C₈) was used as acyl donor. Synthesized compounds were purified and evaluated for their antioxidant activity using the DPPH and the ABTS tests. Results showed that esterification had little effect on radical-scavenging capacity. However, long chain fatty acid esters displayed higher protective effect of oil against oxidation at 70 °C as compared to the parent dopamine or to the BHT. The hemolytic activity of dopamine esters was studied. Middle chain length derivatives (DA-C₈ and DA-C₁₂) of dopamine and oleic acid derivative (DA-C_18:1) showed the highest hemolytic activity against human erythrocyte. The antimicrobial activities of dopamine esters were also evaluated using well diffusion and minimal inhibition concentration methods. Among all the tested compounds, DA-C₈ and DA-C₁₂ exhibited the highest antibacterial activities. These results open up potential applications by using dopamine derivatives as antioxidants and antimicrobial compounds in cosmetic, food and pharmaceutical industries.     

Synthesis of new morpholine-connected pyrazolidine derivatives and their antimicrobial,antioxidant, and cytotoxic activities

A simple and convenient one-pot four-component synthesis of morpholine-connected pyrazolidine derivatives 2a–f and 4a–f was developed using direct metal-free catalysis, with the identities of the synthesized compounds confirmed by IR, NMR (¹H and ¹³C), mass spectrometry, and elemental analysis. The prepared compounds were inspected for antimicrobial, antioxidant, and cytotoxic activities.Antimicrobial and antifungal activities against five bacterial and four fungal pathogens, respectively, were investigated using the disc diffusion technique. In antibacterial activity, compounds 2d and 2f (MIC = 2 μg/mL) exhibited significantly higher activity than the standard ciprofloxacin. The results of antifungal assay showed that the activity of compound 4a (MIC = 0.5 μg/mL) was significantly higher than the standard clotrimazole. Antioxidant activity was screened based on ABTS⁺ radical scavenging and linoleic acid peroxidation performance. Compound 4a showed substantial antioxidant (91.3%) activities, as compared with the Trolox standard. Cytotoxicity was evaluated using HepG2 (liver), HeLa (cervical), and MCF-7 (breast) cancer cell lines, with high toxicities observed for 2b (GI₅₀ = 12.2 μm) and 4a (GI₅₀ = 07.8 μm).     

Anti-HIV and antiplasmodial activity of original flavonoid derivatives

In our search for potent anti-HIV and antiplasmodial agents, novel series of flavonoid derivatives and their chalcone intermediates were synthesized and evaluated for inhibition of HIV multiplication and antiproliferative activity on Plasmodium falciparum parasites. Chalcones exhibited a more selective antiplasmodial activity than flavonoids. Methoxyflavone 7e was the only one compound active in both P. falciparum and HIV-1 whereas aminomethoxyflavones showed activity against HIV-2. Para substitution on the B ring seemed to increase HIV-2 potency.     

水杨酸酰化对胭脂萝卜天竺葵素稳定性和抗氧化活性的影响

为探究水杨酸作为酰化剂对胭脂萝卜天竺葵素的稳定性和抗氧化活性的影响,以保留率为指标,分析光、温度、金属离子、pH及氧化剂对酰化天竺葵素稳定性的影响,探究酰化天竺葵素对羟自由基、DPPH自由基和ABTS自由基的清除能力。结果表明:酰化天竺葵素对光、温度、Al3+、pH的稳定性显著提高,对Fe2+、Mg2+和Zn2+以及氧化剂H2O2的稳定性无显著差影响。酰化天竺葵素对羟自由基、DPPH自由基和ABTS自由基的清除能力与未酰化天竺葵素无显著差异。以上结果表明采用水杨酸酰化胭脂萝卜天竺葵素不影响其抗氧化活性,还能提高其对光照、温度、pH及铝离子的稳定性。     

On the occurrence of acylated flavonoid aglycones

The known acylated flavonoid aglycones are reviewed. Their substitution patterns and their distribution in plants are discussed briefly. A new pair of flavonol esters is reported in Notholaena candida var. candida, the acetate and butyrate of isognaphalin.     

The preparation and antioxidant activity of the sulfanilamide derivatives of chitosan and chitosan sulfates

Chitosan (CS) and chitosan sulfates (CSS) with different molecular weight (Mw) were reacted with 4-acetamidobenzene sulfonyl chloride to obtain sulfanilamide derivatives of chitosan and chitosan sulfates (LSACS, HSACS, LSACSS, HSACSS). The preparation conditions such as different reaction time, temperature, solvent, and the molar ratio of reaction materials are discussed in this paper. Their structures were characterized by FTIR spectroscopy and elemental analyses. The antioxidant activities of the derivatives were investigated employing various established in vitro systems, such as hydroxyl-radical ((*)OH) superoxide anion (O2(*-)) scavenging and reducing power. All kinds of the compounds (HCS, LCS, HCSS, LCSS, HSACS, LSACS, HSACSS, LSACSS) showed stronger scavenging activity on hydroxyl radical than ascorbic acid (Vc). The inhibitory activities of the derivatives toward superoxide radical by the PMS-NADH system were obvious. The experiment showed that the superoxide radical scavenging effect of sulfanilamide derivatives of chitosan and chitosan sulfates was stronger than that of original CS and CSS. All of the derivatives were efficient in the reducing power. The results indicated that the sulfanilamide group were grafted on CS and CSS increased the reducing power of them obviously.     

Stigmastane derivatives from the roots of Vernonia guineensis and their antimicrobial activity

Chemical investigation of the roots of Vernonia guineensis (Asteraceae) afforded a new stigmastane derivative, vernoguinoside A (1) and the known vernoguinoside (2), stigmasterol 3-O-β-d-glucoside (3) and sitosterol 3-O-β-d-glucoside (4). Their structures were elucidated by spectroscopic analysis. Antimicrobial activities of 1–3 and CH₂Cl₂–MeOH (1:1) extract were evaluated against three bacteria species (Salmonella typhi, Staphylococcus aureus and Shigella flexneri) and three yeasts species (Candida albicans, Candida parapsilosis and Cryptococcus neoformans). Compounds 1 and 2 exhibited both antibacterial and antifungal activities that varied between the microbial species (MIC = 7.81–125 μg/mL) while S. flexneri and C. albicans were sensitive to all the tested compounds.     

Novel enzymatic approach to the synthesis of flavonoid glycosides and their esters

Flavonoids such as (+)catechin can be efficiently solubilised in supersaturated solutions prepared with donor glycosides, e.g., p-nitrophenyl glycosides, di- and higher oligosaccharides, and poly(ethylene glycol) dimethyl ether in sufficiently high concentration for their efficient enzymatic glycosylation. Under these conditions several glycosidases readily accept (+)catechin as substrate and the target glycosides were prepared in one step in up to 26% yields. The regioselectivity of the reaction depends on the enzyme and substrate combination used; three positions, 5, 7, and 4', in the flavonoid can be glycosylated. The resulting and similar flavonoid glycosides were further modified by regioselective acylation with vinyl esters of arylpropenoic acids using lipases as biocatalyst. The efficiency of acylation was found to diminish in the order of vinyl cinnamate > vinyl ferulate > vinyl coumarate. This work demonstrates the feasibility of assembling complex flavonoid glycoside esters in just two steps by sequential use of commercially available glycosidases and lipases.