Maleic Acid Derivatives Research Articles

Extraction, isolation, identification, and bioactivity of polysaccharides from Antrodia cinnamomea

Antrodia (A) cinnamomea is a precious edible and medicinal mushroom and has attracted attention because of its rare resources and unique bioactivities. The bioactive compounds from the fruit body, mycelium, and fermentation broth of A. cinnamomea include triterpenoids, polysaccharides, antroquinonols, benzenoids, and succinic and maleic acid derivatives. Among these, polysaccharides are very important and are high-content bioactive compounds. The A. cinnamomea polysaccharides (APSs) present numerous biological activities, such as antiviral, anticancer, anti-inflammatory, antivascular, immunoregulation, antioxidant, and nerve protection. However, only few studies have focused only on APSs so far. Therefore, the cultivation methods, extraction, isolation, composition, structure, biological activity, and application of APSs are summarized in this review to provide a comprehensive and convenient reference for further research and development on APSs.

Synthesis of functionalized spirocyclic oxetanes through Paternò-Büchi reactions of cyclic ketones and maleic acid derivatives.

A telescoped three-step sequence to functionalised spirocyclic oxetanes is reported, involving Paternò-Büchi reactions between maleic acid derivatives and cyclic ketones. p-Xylene suppresses the competing alkene dimerization that has plagued previous work, allowing access to 35 novel spirocyclic oxetanes that cannot be prepared using existing methodologies, and which represent versatile intermediates for further elaboration.

Mono-n-butyl Malate-Derived Compounds from Camu-camu (Myrciaria dubia) Malic Acid: The Alkyl-Dependent Antihyperglycemic-Related Activity.

Malic acid derivatives from camu-camu (Myrciaria dubia) fruit exhibited a strong in vitro inhibitory activity toward pancreatic α-amylase and α-glucosidase enzymes. During a bioguided chromatographic fractionation process of the whole fruit (pulp and peelings) polar extract, isomers (S)-4-butoxy-2-hydroxy-4-oxobutanoic acid (1) and (S)-4-butoxy-3-hydroxy-4-oxobutanoic acid (2) (84:16) were isolated and identified as a potent inhibitor of α-amylase (IC50= 11.69 ± 1.75 μg/mL) and α-glucosidase (IC50 = 102.69 ± 4.16 μg/mL). The chemical structures were confirmed by HPLC-ESIMS and 1H and 13C NMR (one- and two-dimensional) analyses. The structure-based virtual screening demonstrated that the aliphatic moiety plays a significant role in the binding mode of the test alkyl malate esters. Compound 1 exhibited the best interaction profile to bind both enzymes, having key structural features to form relevant contacts by involving adequate enzyme-ligand complex stabilization and compactness over time.

Diene-transmissive hetero-Diels–Alder reaction of distyryl thioketone

The reaction distyryl thioketone with donor alkenes (norbornene and styrene) gives adducts of the hetero-Diels–Alder reaction. In the case of maleic acid derivatives, a tandem reaction occurs which leads to polycyclic derivatives of 3,4-dihydro-2H-thiopyran. The stereochemical features of the ongoing transformations were examined.

Dichloro Butenediamides as Irreversible Site-Selective Protein Conjugation Reagent.

We describe maleic‐acid derivatives as robust cysteine‐selective reagents for protein labelling with comparable kinetics and superior stability relative to maleimides. Diamide and amido‐ester derivatives proved to be efficient protein‐labelling species with a common mechanism in which a spontaneous cyclization occurs upon addition to cysteine. Introduction of chlorine atoms in their structures triggers ring hydrolysis or further conjugation with adjacent residues, which results in conjugates that are completely resistant to retro‐Michael reactions in the presence of biological thiols and human plasma. By controlling the microenvironment of the reactive site, we can control selectivity towards the hydrolytic pathway, forming homogeneous conjugates. The method is applicable to several scaffolds and enables conjugation of different payloads. The synthetic accessibility of these reagents and the mild conditions required for fast and complete conjugation together with the superior stability of the conjugates make this strategy an important alternative to maleimides in bioconjugation.

Synthesis of Poly(Malic Acid) Derivatives End-Functionalized with Peptides and Preparation of Biocompatible Nanoparticles to Target Hepatoma Cells.

Recently, short synthetic peptides have gained interest as targeting agents in the design of site-specific nanomedicines. In this context, our work aimed at developing new tools for the diagnosis and/or therapy of hepatocellular carcinoma (HCC) by grafting the hepatotropic George Baker (GB) virus A (GBVA10-9) and Plasmodium circumsporozoite protein (CPB)-derived peptides to the biocompatible poly(benzyl malate), PMLABe. We successfully synthesized PMLABe derivatives end-functionalized with peptides GBVA10-9, CPB, and their corresponding scrambled peptides through a thiol/maleimide reaction. The corresponding nanoparticles (NPs), varying by the nature of the peptide (GBVA10-9, CPB, and their scrambled peptides) and the absence or presence of poly(ethylene glycol) were also successfully formulated using nanoprecipitation technique. NPs were further characterized by dynamic light scattering (DLS), electrophoretic light scattering (ELS) and transmission electron microscopy (TEM), highlighting a diameter lower than 150 nm, a negative surface charge, and a more or less spherical shape. Moreover, a fluorescent probe (DiD Oil) has been encapsulated during the nanoprecipitation process. Finally, preliminary in vitro internalisation assays using HepaRG hepatoma cells demonstrated that CPB peptide-functionalized PMLABe NPs were efficiently internalized by endocytosis, and that such nanoobjects may be promising drug delivery systems for the theranostics of HCC.

SYNTHESIS OF META-ALTERED ARYLMALEINAMIDE AND PREPARATION OF ESTERS IN THEIR PRESENCE

The development of new methods of synthesis using cheaper reagents for the preparation of maleic acid derivatives, the study of chemical properties and the determination of new directions for the practical application of maleic acid derivatives are still relevant. Therefore, the development of this work is an urgent task. The aim of this study was to obtain the synthesis of monomaleinamide compounds under various conditions to obtain arylmaleimide derivatives of maleic acid and to transfer them in a pure state for further reactions. In this study, scientific studies were carried out to find convenient methods for the preparation of monoamide compounds of maleic acid based on equimolar reactions of aromatic monoamines with functional groups -OH, -COOH, -NO2 with maleic anhydride and maleic acid in the meta-state, and the reaction conditions were analyzed. The relative activity of amines in nucleophilic binding reactions is following an order: (-OH <-COOH <-NO2). According this order, the m-nitroaniline was found to be more active in reaction. The proposed methods were used to study the effect of solvents (dioxane, acetone, DMF, ethanol) on the reaction of monoarylamines with maleic anhydride, as well as on the reaction with maleic acid (acetone, glacial acetic acid) and the effect of different temperatures on the reaction yield. discovered. Aproton showed high yields in the reaction of the solvent with acetone. As a result of the reactions of esterification of arylmaleinamides with methanol and ethanol, the corresponding esters were synthesized. The structure of the obtained compounds was confirmed by IR-, 1H NMR-spectroscopy, gas chromatography-mass spectrometry (GC-MS) and other methods. The level of activity of N-(3-hydroxyphenyl)maleinamide against some microorganisms was studied

Chemical composition and microencapsulation suitability of sumac (Rhus coriaria L.) fruit extract

Sumac (Rhus coriaria L.), a spice obtained by grinding whole sumac berries, is a complex natural product with a plethora of biological activities that can be favorably explored in nutraceutical and pharmaceutical fields. Sicilian sumac is herein chemically investigated by means of a combined NMR/HR MS-based profiling. A hydroalcoholic extract was prepared and its complexity unraveled following fractionation in an alcoholic and an aqueous fraction. The 1H-NMR spectrum of this latter fraction was dominated by the signals of gallic acid and its derivatives, whereas HR MS and HR MS/MS analyses highlighted the diversity in malic acid derivatives. Gallotannins and galloyl flavonol glycosides with quercetin and myricetin as the main aglycones were highly represented in the alcoholic fraction. To improve bioavailability of chemicals in sumac extract, the feasibility of a microencapsulation process by spray drying was investigated. In particular, the addition of maltodextrin, cyclodextrin and gum arabic as covering agents was evaluated. The tests were carried out at different temperatures and concentrations. The addition of maltodextrin was found to be suitable as a carrier for the spray drying of sumac extract, having the highest yields, always > 82%. The highest values of a* (red index) and Chroma were recorded with cyclodextrin and maltodextrin at the lowest concentrations and temperatures of spray drying (120 °C). The correlations between the characteristics of the studied microcapsules (yields, moisture, total and surface polyphenols and colour) have been represented by Principal Component Analysis (PCA).

Synthesis and ethylene-promoted metathesis of adducts of tandem [4+2]/[4+2] cycloaddition between bis-furyl dienes and maleic acid derivatives

A series of 1,4:5,8-diepoxynaphthalenes, annellated with carbo- and heterocycles, was synthesized based on the tandem intermolecular/intramolecular [4+2] cycloaddition of bis-furyl dienes with moderately to highly reactive cyclic dienophiles (maleic anhydride and maleinimides).

Medicinal plant of Bletilla striata: A review of its chemical constituents, pharmacological activities, and quality control

Bletilla striata belongs to the family Orchidaceae, and it is mainly distributed in East Asia. The tubers of B. striata have been utilized in Traditional Chinese Medicine for various ailments, such as hematemesis, tuberculosis, malignant ulcers, hemorrhoids, traumatic bleeding, and chapped skin. Phytochemical investigation on B. striata has resulted in the identification of 192 monomeric compounds, including bibenzyls, phenanthrene derivatives, triterpenoids and its saponins, steroids and its saponins, malic acid derivatives, and anthocyanins. Moreover, B. striata polysaccharide is another typical chemical constituent of this plant. Pharmacology studies have shown that the plant possesses wound healing, antimicrobial, anticancer, antioxidative, and antiviral activities. This review aims to provide the latest and comprehensive information on chemical constituents, pharmacological activities, and quality control of B. striata and to identify future research needs.

A convenient synthesise of 3,4-dihydro-2H-thiopyran-2,3-dicarboxylic acid derivatives

A three-component one-pot procedure to synthesize 2,4-disubstituted b-fused 3,4-dihydro-2H-thiopyran derivatives by the Diels—Alder reaction of the in situ generated α,β-enethiones with maleic acid derivatives was developed. The reactivity of different unsaturated thioketones as dienes and maleic acid derivatives as dienophiles under the developed reaction conditions was studied.

Synthesis and characterization of cassava starch with maleic acid derivatives by etherification reaction

Cassava starch was grafted with three different esters by the etherification reaction and its modification was characterized by 1H NMR, FTIR, DSC, SEM, XDR, contact angle and SLS. The samples grafted with diethyl maleate, dipropyl maleate, and dibutyl maleate showed DS values of 2.3, 1.0 and 2.0, respectively, determined from 1H NMR analysis and confirmed by FTIR analysis, with the appearance of bands at 1721, 1550 and 1126cm−1. The FTIR, XRD, SEM and DSC results indicated a change in the intra and intermolecular hydrogen interactions in the grafted starch when compared to native starch. Based on the contact angles, it was observed that the macromolecular starch chain acquired hydrophobic characteristics through the substitution of the hydrogens with di maleate esters. The characteristics acquired by grafted starch allow it to be used for the encapsulation of bioactive molecules for the production of bioactive packages and the production of biodegradable packages.

Polyphenolic profile of green/red spotted Italian Cichorium intybus salads by RP-HPLC-PDA-ESI-MSn

Today the consumption of fresh vegetables is highly recommended not only for the intake of nutrients, but also for the healthy properties of secondary metabolites involved in the prevention of many disorders. In the present work, phenolic acids and flavonoids extracted from four green (Cichorium intybus var. sativus and var. foliosum) and a red spotted (a cross between C. intybus var. silvestre cv “Treviso” and C. endivia var. foliosum) salads were characterized by high-performance liquid chromatography–electrospray ionization/mass spectrometry. Among the 76 compounds detected in this work, five organic acids (two malic acid derivatives, two pyroglutamic hexoside isomers, and cis-aconitic acid), ten hydroxycinnamic acid derivatives (ferulic, malonyl caffeoylquinic, and caffeoylmethylglutaroylquinic acids, cinnamoyl- and caffeoyl-malate, coumaroyl, sinapoyl, feruloyl, and coumaroylcaffeoyl glycosides, dicaffeoyl lactone, 3-O-caffeoyl-4-O-(3-hydroxyglutaroylquinic acid), four flavonols (quercetin-di-O-glucoside, quercetin-3-O-malonylhexosyl-7-O-hexoside, myricetin-3-O-glucoside, and isorhamnetin-3-O-glucoside), and cyanidin-3-O-glucuronyl-5-O-hexoside have been identified in chicory salads for the first time. These data, together with the results obtained in our previous investigations on Cichorium genus Italian salads, provide a contribution to a more exhaustive identification of the secondary metabolites profile of each considered plant, that could be also useful in building/selecting hybrids with agronomic and peculiar healthy features, even using traditional methods of cultivation.

In Vitro Anticancer Activity and Structural Characterization of Ubiquinones from Antrodia cinnamomea Mycelium.

Two new ubiquinones, named antrocinnamone and 4-acetylantrocamol LT3, were isolated along with six known ubiquinones from Antrodia cinnamomea (Polyporaceae) mycelium. The developed HPLC analysis methods successfully identified eight different ubiquinones, two benzenoids, and one maleic acid derivative from A. cinnamomea. The ubiquinones 1–8 exhibited potential and selective cytotoxic activity against three human cancer cell lines, with IC50 values ranging from 0.001 to 35.883 μM. We suggest that the different cytotoxicity levels were related to their chemical structures, especially the 4-hydroxycyclohex-2-enone ring and the presence of a free hydroxyl group in the side chain. The suppression by 4-acetylantrocamol LT3 stopped the cell cycle at the beginning of the G2-M phase thus making the cell cycle arrest at the sub-G1 phase as compared with control cells.

UV and γ-ray resistance of poly(N-methylmaleimide-alt-isobutene) and poly(diisopropyl fumarate) as transparent polymer films

UV and γ-ray resistance of transparent polymers obtained by radical polymerization of maleic and fumaric acid derivatives, i.e., an alternating copolymer of N-methylmaleimide and isobutene (PMI) and poly(diisopropyl fumarate) (PDiPF), was investigated. Transmittance in UV and visible regions of these polymers were examined after UV irradiation and compared with the results for poly(methyl methacrylate) (PMMA) and polycarbonate (PC) as conventional transparent polymers. The order of stability toward UV irradiation was PMMA≈PDiPF>PMI>>PC, deduced from changes in the transmittance of 380nm light. Tensile mechanical properties, such as elastic modulus, maximum strength, and elongation values of PMI, PDiPF, and PMMA were also investigated after UV and γ-radiation. UV irradiation induced the side chain scission of PMI and PDiPF via Norrish I type reaction as well as crosslinking by combination between formed polymer radicals, leading to deterioration in their optical and mechanical properties. γ-radiation induced significant changes in molecular weight and mechanical properties of the polymers. In conclusion, PMI exhibited unchanged mechanical properties and PDiPF maintained its high transparency under various irradiation conditions.

Poly(malic acid) bearing Doxorubicin and N-Acetyl Galactosamine as a site-specific prodrug for targeting hepatocellular carcinoma

In the past, several systems of drug delivery carriers have been designed with a high capacity to target specific cells and/or tissues and a reduced non-specific toxicity. In this context, we synthesized and characterized novel poly(malic acid) derivatives bearing Doxorubicin (Dox), Poly(ethylene glycol) (PEG) and/or N-Acetyl Galactosamine (NAcGal) for drug delivery. These poly(malic acid) derivatives were obtained by chemical modification of the carboxylic acid lateral groups of poly(malic acid) (PMLA). The resulting nanoplatforms were evaluated for their in vitro cytotoxicity using the human HepaRG hepatoma cell line. Results reveal that the PMLA nanoplatform modified with PEG and Dox has an IC50 of 936 nM corresponding to a Dox concentration of 47 nM, while the grafting of NAcGal onto the nanoplatform reduced the IC50 to 527 nM corresponding to a Dox concentration of 26 nM. The presence of the targeting moiety, NAcGal, thus improves the cellular toxicity of the Dox.

Prevention of TGF-β-induced early liver fibrosis by a maleic acid derivative anti-oxidant through suppression of ROS, inflammation and hepatic stellate cells activation.

Current anti-fibrotic effect of antioxidants in vivo is disappointing due probably to the fact that once liver fibrogenesis is established it is too advanced to be reversed by anti-oxidation mechanism. We consider antioxidant may only act on the early phase of fibrogenesis. Thus, we had previously established an early liver fibrosis animal model using an inducible expression vector (pPK9a), which contains TGF-β gene and was hydro-dynamically transferred into mice to induce a transient liver fibrosis. TGF-β1 has been well documented to up-regulate the expression of α2(1) collagen (Col 1A2) gene in the liver via the reactive oxygen species (ROS); the process triggers inflammation, leading to hepatic stellate cells (HSC) activation and liver fibrogenesis. Using our animal model and ROS, cyclooxygenase-2 (Cox-2) and Col 1A2 promoter assays as screening targets, we report here that a maleic acid derivative isolated from the Antrodia camphorata mycelium strongly decreases ROS production, promoter activity of Cox-2 and Col 1A2, intracellular calcium, expression of alpha-smooth muscle actin (α-SMA), Smad4-p-Smad2/3 co-localization in cell nucleus and the DNA binding activity of Sp1. Our results suggest that the maleic acid derivative prevents liver fibrosis at an early phase both in vitro and in vivo through the inhibition of ROS, inflammation and the activation of HSC.

Phenolic compounds from Bletilla striata

Two new malic acid derivatives, namely eucomic acid 1-methyl ester (2) and 6′′′-acetylmilitaline (7), together with ten known compounds (1, 3–6, 8–12), were isolated from the dry tubers of Bletilla striata (Thunb.) Reichb. F., a perennial traditional Chinese medicinal herb, which was used for the treatment of pneumonophthisis, pneumonorrhagia, tuberculosis, and hemorrhage of the stomach or lung. Their structures were elucidated by spectroscopic analyses, including 1D-, 2D-NMR, and HR-ESI-MS.

Synthesis and some properties of complexones, succinic acid derivatives

Approaches to the synthesis of complexones, succinic acid derivatives, from maleic acid and amino derivatives were considered. Acid-base properties of these complexones were studied.

Oxidative Alkoxycarbonylation of Alkynes by Means of Aryl α‐Diimine Palladium(II) Complexes as Catalysts

AbstractThe straightforward in situ synthesized bis(2,6‐diisopropyl)acenaphthenequinonediimine palladium triflate catalyst was generally employed for both the mono‐alkoxycarbonylation of terminal alkynes, and the bis‐alkoxycarbonylation of 1,2‐disubstituted alkynes by using mild reaction conditions [carbon monoxide pressure (PCO)=4 bar, temperature=20 °C]. Utilizing low catalyst loading (down to 0.5 mol%), a variety of propiolic esters were synthesized with good to excellent isolated yields. Most importantly the system was very efficient not only with methanol but also with a range of different alcohols, starting from the less hindered benzyl alcohol to the most hindered ones, such as isopropyl alcohol and tert‐butyl alcohol. In addition, aromatic and aliphatic 1,2‐disubstituted alkynes were converted into maleic acid derivatives, together with an acid‐catalyzed isomerization reaction, showing modest to good selectivity and excellent combined yields. In particular 3‐hexyne showed a satisfactory degree of selectivity for the maleic diesters of methanol and benzyl alcohol, obtaining the corresponding products with good isolated yields.magnified image