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Bracken fern (Pteridium spp.) is a highly problematic plant worldwide due to its toxicity in combination with invasive properties on former farmland, in deforested areas and on disturbed natural habitats. The carcinogenic potential of bracken ferns has caused scientific and public concern for six decades. Its genotoxic effects are linked to illudane-type glycosides (ITGs), their aglycons and derivatives. Ptaquiloside is considered the dominating ITG, but with significant contributions from other ITGs. The present review aims to compile evidence regarding environmental pollution by bracken fern ITGs, in the context of their human and animal health implications. The ITG content in bracken fern exhibits substantial spatial, temporal, and chemotaxonomic variation. Consumption of bracken fern as food is linked to human gastric cancer but also causes urinary bladder cancers in bovines browsing on bracken. Genotoxic metabolites are found in milk and meat from bracken fed animals. ITG exposure may also take place via contaminated water with recent data pointing to concentrations at microgram/L-level following rain events. Airborne ITG-exposure from spores and dust has also been documented. ITGs may synergize with major biological and environmental carcinogens like papillomaviruses and Helicobacter pylori to induce cancer, revealing novel instances of chemical and biological co-carcinogenesis. Thus, the emerging landscape from six decades of bracken research points towards a global environmental problem with increasingly complex health implications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The conventional approach to developing light-sensitive glycosidase activity regulators, involving the combination of a glycomimetic moiety and a photoactive azobenzene module, results in conjugates with differences in glycosidase inhibitory activity between the interchangeable E and Z-isomers at the azo group that are generally below one-order of magnitude. In this study, we have exploited the chemical mimic character of sp 2 -iminosugars to access photoswitchable p- and o-azobenzene α-O-glycosides based on the gluco-configured representative ONJ. Notably, we achieved remarkably high switching factors for glycosidase inhibition, favoring either the E- or Z-isomer depending on the aglycone structure. Our data also indicate a correlation between the isomeric state of the azobenzene module and the selectivity towards α- and β-glucosidase isoenzymes. The most effective derivative reached over a 10 3 -fold higher inhibitory potency towards human β-glucocerebrosidase in the Z as compared with the E isomeric form. This sharp contrast is compatible with ex-vivo activation and programmed self-deactivation at physiological temperatures, positioning it as a prime candidate for pharmacological chaperone therapy in Gaucher disease. Additionally, our results illustrate that chemical tailoring enables the engineering of photocommutators with the ability to toggle inhibition between α- and β-glucosidase enzymes in a reversible manner, thus expanding the versatility and potential therapeutic applications of this approach., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

The reagent system based on the combined use of Et 3 SiH/I 2 acts as an efficient N -glycosidation promoter for the synthesis of natural and sugar-modified nucleosides. An analysis of reaction stereoselectivity in the absence of C2-positioned stereodirecting groups revealed high selectivity with six-membered substrates, depending on the nucleophilic character of the nucleobase or based on anomerization reactions. The synthetic utility of the Et 3 SiH/I 2 -mediated N -glycosidation reaction was highlighted by its use in the synthesis of the investigational drug apricitabine.

Introduction: Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra. The precise molecular mechanisms underlying neuronal loss in PD remain unknown, and there are currently no effective treatments for PD-associated neurodegeneration. Echinacoside (ECH) is known for its neuroprotective effects, which include scavenging cellular reactive oxygen species and promoting mitochondrial fusion. However, the blood-brain barrier (BBB) limits the bioavailability of ECH in the brain, posing a significant challenge to its use in PD treatment., Methods: We synthesized and characterized PEGylated ECH liposomes (ECH@Lip) and peptide angiopep-2 (ANG) modified liposomes (ECH@ANG-Lip). The density of ANG in ANG-Lip was optimized using bEnd.3 cells. The brain-targeting ability of the liposomes was assessed in vitro using a transwell BBB model and in vivo using an imaging system and LC-MS. We evaluated the enhanced neuroprotective properties of this formulation in a the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model., Results: The ECH@ANG-Lip demonstrated significantly higher whole-brain uptake compared to ECH@Lip and free ECH. Furthermore, ECH@ANG-Lip was more effective in mitigating MPTP-induced behavioral impairment, oxidative stress, dopamine depletion, and dopaminergic neuron death than both ECH@Lip and free ECH., Conclusion: The formulation used in our study significantly enhanced the neuroprotective efficacy of ECH in the MPTP-induced PD model. Thus, ECH@ANG-Lip shows considerable potential for improving the bioavailability of ECH and providing neuroprotective effects in the brain., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Ou et al.)

DNA glycosidic bond cleavage may induce cancer under the ultraviolet (UV) effect. Yet, the mechanism of glycosidic bond cleavage remains unclear and requires more detailed clarification. Herein, quantum chemical studies on its photoinduced mechanism are performed using a 5'-thymidine monophosphate (5'-dTMPH) model. In this study, four possible paths were examined to study the glycosidic bond cleavage. The results showed that, upon excitation, the electronic transition from the π bonding to π antibonding orbitals of the thymine ring leads to the damage of the thymine ring. Afterwards, the glycosidic bond is cleaved. At first, the doublet ground state (GS) path of glycosidic bond cleavage widely studied by other groups is caused by free electron generated by photoirradiation, with a kinetically feasible energy barrier of ~23 kcal/mol. Additionally, then, the other three paths were proposed that also might cause the glycosidic bond cleavage. The first one is the doublet excited state (ES) path, triggered by free electron along with UV excitation, which can result in a very-high-energy barrier ~49 kcal/mol that is kinetically unfavorable. The second one is the singlet ES path, induced by direct UV excitation, which assumes DNA is directly excited by UV light, which features a very low-energy barrier ~16 kcal/mol that is favored in kinetics. The third one is the triplet ES path, from the singlet state via intersystem crossing (ISC), which refers to a feasible ~27 kcal/mol energy barrier. This study emphasizes the pivotal role of the DNA glycosidic bond cleavage by our proposed direct UV excitation (especially singlet ES path) in addition to the authorized indirect free-electron-induced path, which should provide essential insights to future mechanistic comprehension and novel anti-cancer drug design.

The latex of Ipomoea (Convolvulaceae) is a source of a special kind of acylsugars called resin glycosides, which are highly appreciated because of their biological activities (i.e. laxative, antimicrobial, cytotoxic etc.). Most research has been conducted in perennials with tuberous roots, where resin glycosides are stored. However, their content and variation are unknown in annual vines that lack this type of root, such as in the case of Ipomoea parasitica. This species contains research/biological and human value through its fast growth, survival in harsh environments, and employment in humans for mental/cognitive improvements. These qualities make I. parasitica an ideal system to profile resin glycosides and their variations in response to edaphoclimate. Topsoil samples (0-30 cm depth) and latex from petioles of I. parasitica were collected in two localities of central Mexico. The latex was analyzed through UHPLC-ESI-QTOF, and soil physico-chemical characteristics, the rainfall, minimum, average, and maximum temperatures were recorded. We also measured canopy (%), rockiness (%), and plant cover (%). A Principal Component Analysis was conducted to find associations between edaphoclimate and the resin glycosides. Forty-four resin glycosides were found in the latex of I. parasitica. Ten correlated significantly with three components (47.07%) and contained tetrasaccharide, pentasaccharide, and dimers of tetrasaccharide units. Five resin glycosides were considered constitutive because they were in all the plants. However, exclusive molecules to each locality were also present, which we hypothesize is in response to significant microhabitat conditions found in this study (temperature, clay content, pH, and potassium). Our results showed the presence of resin glycosides in I. parasitica latex and are the basis for experimentally testing the effect of the conditions above on these molecules. However, ecological, molecular, and biochemical factors should be considered in experiments designed to produce these complex molecules., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Pérez-Sanvicente et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The current study intended to investigate the role of new natural compounds derived from the Sesuvium sesuvioides plant in mitigating symptoms of diabetes and insulin resistance in the diabetic mice model. Anti-advanced glycation activity, insulin, and adiponectin were quantified by enzyme-linked immunosorbent assay (ELISA). Glucose uptake was performed using enzymatic fluorescence assay, and glycogen synthesis was measured using PAS staining. Gene and protein expression was assessed using real time PCR (RT-PCR), and immunoblotting and fluorescent microscopy, respectively. The new flavonoid glycoside eupalitin 3- O -α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside 1 isolated from S. sesuvioides exhibited anti-AGE activity by reducing human glycated albumin in liver cells. In a diabetic mouse model treated with compound 1 , we observed improved glucose tolerance, increased adiponectin levels, and decreased insulin resistance. We also observed alleviated AGEs induced reduction in glucose uptake and restored glycogen synthesis in the compound 1 -treated diabetic mice muscles. Exploring the molecular mechanism of action in skeletal muscle tissue of diabetic mice, we found that 1 reduced AGE-induced reactive oxygen species and the inflammatory gene in the muscle of diabetic mice. Additionally, 1 exhibited these effects by reducing the gene and protein expression of receptor for advanced glycation end products (RAGE) and inhibiting protein kinase C (PKC) delta activation. This further led us to demonstrate that compound 1 reduced serine phosphorylation of IRS-1, thereby restoring insulin sensitivity. We conclude that a new flavonoid glycoside from S. sesuvioides could be a therapeutic target for the treatment of symptoms of insulin resistance and diabetes.

The main purpose of the present study was to determine the effect of associating an optimized ultrasound-assisted extraction (UAE) protocol with enzyme-assisted extraction (EAE) in aqueous media, using the dried berries of Hippophae rhamnoides L. (sea buckthorn) as plant material. A specialized software was used for the determination of potential optimal extraction parameters, leading to the development of four optimized extracts with different characteristics (UAE ± EAE). For these extracts, buffered or non-buffered solutions have been used, with the aim to determine the influence of adjustable pH on extractability. As enzymatic solution, a pectinase, cellulase, and hemicellulase mix (2:1:1) has been applied, acting as pre-treatment for the optimized protocol. The highest extractive yields have been identified for non-buffered extracts, and the E-UAE combination obtained extracts with the highest overall in vitro antioxidant activity. The HPLC-MS n analysis demonstrated a rich composition in different types of isorhamnetin-O-glycosides, as well as some quercetin-O-glycosides, showing a high recovery of specific flavonol-type polyphenolic species. Moreover, we have tentatively identified two flavanols (i.e., catechin and epigallocatechin) and one flavone derivative (i.e., luteolin)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Oligosaccharides have myriad functions throughout biological processes 1,2 . Chemical synthesis of these structurally complex molecules facilitates investigation of their functions. With a dense concentration of stereocentres and hydroxyl groups, oligosaccharide assembly through O-glycosylation requires simultaneous control of site, stereo- and chemoselectivities 3,4 . Chemists have traditionally relied on protecting group manipulations for this purpose 5-8 , adding considerable synthetic work. Here we report a glycosylation platform that enables selective coupling between unprotected or minimally protected donor and acceptor sugars, producing 1,2-cis-O-glycosides in a catalyst-controlled, site-selective manner. Radical-based activation 9 of allyl glycosyl sulfones forms glycosyl bromides. A designed aminoboronic acid catalyst brings this reactive intermediate close to an acceptor through a network of non-covalent hydrogen bonding and reversible covalent B-O bonding interactions, allowing precise glycosyl transfer. The site of glycosylation can be switched with different aminoboronic acid catalysts by affecting their interaction modes with substrates. The method accommodates a wide range of sugar types, amenable to the preparation of naturally occurring sugar chains and pentasaccharides containing 11 free hydroxyls. Experimental and computational studies provide insights into the origin of selectivity outcomes., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Trypanosoma cruzi is the pathogen of Chagas disease, a neglected tropical disease that affects more than 6 million people worldwide. There are no vaccines to prevent infection, and the therapeutic arsenal is very minimal and toxic. The unique E-NTPDase of T. cruzi (TcNTPDase1) plays essential roles in adhesion and infection and is a virulence factor. Quercetin is a flavonoid with antimicrobial, antiviral, and antitumor activities. Its potential as a partial inhibitor of NTPDases has also been demonstrated. In this work, we synthesized the non-natural L-glycoside derivatives of quercetin and evaluated them as inhibitors of recombinant TcNTPDase1 (rTcNTPDase1). These compounds, and quercetin and miquelianin, a natural quercetin derivative, were also tested. Compound 16 showed the most significant inhibitory effect (94%). Quercetin, miquelianin, and compound 14 showed inhibition close to 50%. We thoroughly investigated the inhibitory effect of 16. Our data suggested a competitive inhibition with a Ki of 8.39 μM (± 0.90). To better understand the interaction of compound 16 and rTcNTPDase1, we performed molecular dynamics simulations of the enzyme and docking analyses with the compounds. Our predictions show that compound 16 binds to the enzyme's catalytic site and interacts with important residues for NTPDase activity. As an inhibitor of a critical T. cruzi enzyme, (16) could be helpful as a starting point in the developing of a future treatment for Chagas disease. Furthermore, the discovery of (16) as an inhibitor of TcNTPDase1 may open new avenues in the study and development of new inhibitors of E-NTPDases., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Olive leaves (OLLs) are an exceptional bioresource of natural polyphenols with proven antioxidant activity, yet the applicability of OLL extracts is constrained by the relatively high polarity of the major polyphenols, which occur as glycosides. To overcome this limitation, OLLs were subjected to both hydrothermal and ethanol organosolv treatments, fostered by acid catalysis to solicit in parallel increased polyphenol recovery and polyphenol modification into simpler, lower-polarity substances. After an initial screening of natural organic acids, oxalic acid (OxAc) was found to be the highest-performing catalyst. The extraction behavior using OxAc-catalyzed hydrothermal and ethanol organosolv treatments was appraised using kinetics, while treatment optimization was accomplished by deploying response-surface methodology. The comparative assessment of the composition extracts produced under optimal conditions of residence time and temperature was performed with liquid chromatography-tandem mass spectrometry and revealed that OLLs treated with 50% ethanol/1.5% HCl suffered extensive oleuropein and flavone glycoside hydrolysis, affording almost 23.4 mg hydroxytyrosol and 2 mg luteolin per g dry weight. On the other hand, hydrothermal treatment with 5% OxAc provided 20.2 and 0.12 mg of hydroxytyrosol and luteolin, respectively. Apigenin was in all cases a minor extract constituent. The study presented herein demonstrated for the first time the usefulness of using a natural, food-grade organic acid to perform such a task, yet further investigation is needed to maximize the desired effect.

Hypothesis: Elucidation of the micro-mechanisms of sol-gel transition of gelling glucans with different glycosidic linkages is crucial for understanding their structure-property relationship and for various applications. Glucans with distinct molecular chain structures exhibit unique gelation behaviors. The disparate gelation phenomena observed in two methylated glucans, methylated (1,3)-β-d-glucan of curdlan (MECD) and methylated (1,4)-β-d-glucan of cellulose (MC), notwithstanding their equivalent degrees of substitution, are intricately linked to their unique molecular architectures and interactions between glucan and water., Experiments: Density functional theory and molecular dynamics simulations focused on the electronic property distinctions between MECD and MC, alongside conformational variations during thermal gelation. Inline attenuated total reflection Fourier transform infrared spectroscopy tracked secondary structure alterations in MECD and MC. To corroborate the simulation results, additional analyses including circular dichroism, rheology, and micro-differential scanning calorimetry were performed., Findings: Despite having similar thermally induced gel networks, MECD and MC display distinct physical gelation patterns and molecular-level conformational changes during gelation. The network of MC gel was formed via a "coil-to-ring" transition, followed by ring stacking. In contrast, the MECD gel comprised compact irregular helices accompanied by notable volume shrinkage. These variations in gelation behavior are ascribed to heightened hydrophobic interactions and diminished hydrogen bonding in both systems upon heating, resulting in gelation. These findings provide valuable insights into the microstructural changes during gelation and the thermo-gelation mechanisms of structurally similar polysaccharides., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Two rare 8-hydroxysteroid glycosides (6-7), and their downstream metabolites (1-5) with an unprecedented 6/6/5/5/5-pentacyclic scaffold, together with seven known analogues (8-14) were isolated from the twigs and leaves of Strophanthus divaricatus. Their structures were fully assigned by analysis of the spectroscopic and ECD data, NMR calculations, X-ray crystallographic study, and chemical methods. In addition, the inhibitory effects of 1-14 on liver and lung cancer cell lines were evaluated, and preliminary structure-activity relationship was discussed. Data-independent acquisition (DIA)-based quantitative proteomic analysis and biological verification of H1299 cells suggested that this family of compounds may play an anticancer role by suppressing both DNA damage response (DDR) and mTOR/S6K signaling pathways., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The whole Hypericum patulum Thunb. plant is utilized in traditional medicine for its properties of clearing heat, detoxifying, soothing meridians, relaxing the liver, and stopping bleeding. In folk medicine, it is frequently used to treat hepatitis, colds, tonsillitis, and bruises. Phytochemical investigation of a 30% ethanol extract of the fresh ripe fruits of H. patulum has resulted in the isolation of two new pinane-type monoterpenoid glycosides 1 - 2 , named patulumside E-F, and three new chain-shaped monoterpenoid glycosides 3 - 5 , named patulumside G-H, J. Their structures were determined using extensive spectroscopic techniques, such as HR-ESI-MS, 1D and 2D NMR spectroscopy, and electronic circular dichroism (ECD) calculation. The anti-inflammatory activities of these compounds were evaluated in the LPS-induced RAW264.7 cells. This research represents the inaugural comprehensive phytochemical study of H. patulum , paving the way for further exploration of monoterpenoid glycosides.

Eight sulfated triterpene glycosides, peronioside A ( 1 ) and psolusosides A ( 2 ), B ( 3 ), G ( 4 ), I ( 5 ), L ( 6 ), N ( 7 ) and P ( 8 ), were isolated from the sea cucumber Psolus peronii . Peronioside A ( 1 ) is a new glycoside, while compounds 2 - 8 were found previously in Psolus fabricii , indicating the phylogenetic and systematic closeness of these species of sea cucumbers. The activity of 1 - 8 against human erythrocytes and their cytotoxicity against the breast cancer cell lines MCF-7, T-47D and triple-negative MDA-MB-231 were tested. The most active against cancer cell compounds, psolusosides A ( 2 ) and L ( 6 ), which were not cytotoxic to the non-transformed cells of the mammary gland, were chosen to study the inhibition of the migration, formation and growth of colonies of the cancer cell lines. Glycoside 2 effectively inhibited the growth of colonies and the migration of the MDA-MB-231 cell line. Compound 6 blocked the growth of colonies of T-47D cells and showed a pronounced antimigration effect on MDA-MB-231 cells. The quantitative structure-activity relationships (QSAR) indicated the strong impact on the activity of the form and size of the molecules, which is connected to the length and architecture of the carbohydrate chain, the distribution of charge on the molecules' surface and various aspects of hydrogen bond formation, depending on the quantity and positions of the sulfate groups. The QSAR calculations were in good accordance with the observed SAR tendencies.

Three new monosulfated polyhydroxysteroid glycosides, spiculiferosides A ( 1 ), B ( 2 ), and C ( 3 ), along with new related unsulfated monoglycoside, spiculiferoside D ( 4 ), were isolated from an ethanolic extract of the starfish Henricia leviuscula spiculifera collected in the Sea of Okhotsk. Compounds 1 - 3 contain two carbohydrate moieties, one of which is attached to C-3 of the steroid tetracyclic core, whereas another is located at C-24 of the side chain of aglycon. Two glycosides ( 2 , 3 ) are biosides, and one glycoside ( 1 ), unlike them, includes three monosaccharide residues. Such type triosides are a rare group of polar steroids of sea stars. In addition, the 5-substituted 3-OSO 3 -α-L-Araf unit was found in steroid glycosides from starfish for the first time. Cell viability analysis showed that 1 - 3 (at concentrations up to 100 μM) had negligible cytotoxicity against human embryonic kidney HEK293, melanoma SK-MEL-28, breast cancer MDA-MB-231, and colorectal carcinoma HCT 116 cells. These compounds significantly inhibited proliferation and colony formation in HCT 116 cells at non-toxic concentrations, with compound 3 having the greatest effect. Compound 3 exerted anti-proliferative effects on HCT 116 cells through the induction of dose-dependent cell cycle arrest at the G2/M phase, regulation of expression of cell cycle proteins CDK2, CDK4, cyclin D1, p21, and inhibition of phosphorylation of protein kinases c-Raf, MEK1/2, ERK1/2 of the MAPK/ERK1/2 pathway.

In Vietnam, the stems and roots of the Rutaceous plant Paramignya trimera (Oliv.) Burkill (known locally as "Xáo tam phân") are widely used to treat liver diseases such as viral hepatitis and acute and chronic cirrhosis. In an effort to search for Vietnamese natural compounds capable of inhibiting coronavirus based on molecular docking screening, two new dimeric coumarin glycosides, namely cis-paratrimerin B (1) and cis-paratrimerin A (2), and two previously identified coumarins, the trans-isomers paratrimerin B (3) and paratrimerin A (4), were isolated from the roots of P. trimera and tested for their anti-angiotensin-converting enzyme 2 (ACE-2) inhibitory properties in vitro. It was discovered that ACE-2 enzyme was inhibited by cis-paratrimerin B (1), cis-paratrimerin A (2), and trans-paratrimerin B (3), with IC 50 values of 28.9, 68, and 77 µM, respectively. Docking simulations revealed that four biscoumarin glycosides had good binding energies (∆G values ranging from -10.6 to -14.7 kcal/mol) and mostly bound to the S1' subsite of the ACE-2 protein. The key interactions of these natural ligands include metal chelation with zinc ions and multiple H-bonds with Ser128, Glu145, His345, Lys363, Thr371, Glu406, and Tyr803. Our findings demonstrated that biscoumarin glycosides from P. trimera roots occur naturally in both cis- and trans-diastereomeric forms. The biscoumarin glycosides Lys363, Thr371, Glu406, and Tyr803. Our findings demonstrated that biscoumarin glycosides from P. trimera roots hold potential for further studies as natural ACE-2 inhibitors for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Background: Many phenolic C-glycosides possess nutritional benefits and pharmacological efficacies. However, the MS/MS fragmentation pattern of phenolic C-glycosides analysis is understudied. This paper aims to determine the MS/MS fragmentation patterns of phenolic C-glycosides., Method: Ten compounds with different sugar moieties, aglycones, and substitutes were analyzed to determine the impact of these structural features on MS/MS fragmentation using UPLC-QTOF-MS analysis., Results: The results showed that water loss followed by RDA reaction and alpha cleavage in the C-C bonded sugar moieties are the major fragmentation pathways. Additionally, the sugar cleavage was not affected by the skeleton and the substitute of the aglycones. These results suggested that the fragmentation patterns of phenolic C-glycosides differ from those in the O-glycosides, where the O-C glycosidic bond is the most cleavage-liable bond in MS/MS analysis., Conclusions: These MS/MS fragmentation patterns can be used for the identification of C-glycosides from dietary components and herbal medicine as well as developing robust methods using MRM methods to quantify C-glycosides.

S -Glycosides are more resistant to enzymatic and chemical hydrolysis and exhibit higher metabolic stability than common O -glycosides, demonstrating their widespread application in biological research and drug development. In particular, β- S -glycosides are used as antirheumatic, anticancer, and antidiabetic drugs in clinical practice. However, the stereoselective synthesis of β- S -glycosides is still highly challenging. Herein, we report an effective β- S -glycosylation using 3- O -trichloroacetimidoyl glycal and thiols under mild conditions. The C3-imidate is designed to guide Pd to form a complex with glucal from the upper face, followed by Pd-S (thiols) coordination to realize β-stereoselectivity. This method demonstrates excellent compatibility with a broad scope of various thiol acceptors and glycal donors with yields up to 87% and a β/α ratio of up to 20:1. The present β- S -glycosylation strategy is used for late-stage functionalization of drugs/natural products such as estrone, zingerone, and thymol. Overall, this novel and simple operation approach provides a general and practical strategy for the construction of β-thioglycosides, which holds high potential in drug discovery and development.

We report the first total synthesis of scleropentaside D, a unique C -glycosidic ellagitannin, from the ketal derivative of scleropentaside A employing site-selective O4-protection of C -acyl glycoside and copper-catalyzed oxidative coupling reaction of galloyl groups as the key steps. Our study confirms the proposed structure of this natural product, scleropentaside D, and demonstrates its effectiveness as an inhibitor of α-glycosidase.

C-1 Glycals serve as pivotal intermediates in synthesizing diverse C-glycosyl compounds and natural products, necessitating the development of concise, efficient and user-friendly methods to obtain C-1 glycosides is essential. The Suzuki-Miyaura cross-coupling of glycal boronates is notable for its reliability and non-toxic nature, but glycal donor stability remains a challenge. Herein, we achieve a significant breakthrough by developing stable glycal boronates, effectively overcoming the stability issue in glycal-based Suzuki-Miyaura coupling. Leveraging the balanced reactivity and stability of our glycal boronates, we establish a robust palladium-catalyzed glycal-based Suzuki-Miyaura reaction, facilitating the formation of various C(sp 2 )-C(sp), C(sp 2 )-C(sp 2 ), and C(sp 2 )-C(sp 3 ) bonds under mild conditions. Notably, we expand upon this achievement by developing the DNA-compatible glycal-based cross-coupling reaction to synthesize various glycal-DNA conjugates. With its excellent reaction reactivity, stability, generality, and ease of handling, the method holds promise for widespread appication in the preparation of C-glycosyl compounds and natural products., (© 2024. The Author(s).)

New sulfonamide-triazole-glycoside hybrids derivatives were designed, synthesised, and investigated for anticancer efficacy. The target glycosides' cytotoxic activity was studied with a panel of human cancer cell lines. Sulfonamide-based derivatives, 4, 7 and 9 exhibited promising activity against HepG-2 and MCF-7 (IC 50  = 8.39-16.90 μM against HepG-2 and 19.57-21.15 μM against MCF-7) comparing with doxorubicin (IC 50  = 13.76 ± 0.45, 17.44 ± 0.46 μM against HepG-2 and MCF-7, rescpectively). To detect the probable action mechanism, the inhibitory activity of these targets was studied against VEGFR-2, carbonic anhydrase isoforms hCA IX and hCA XII. Compoumds 7 and 9 gave favorable potency (IC 50  = 1.33, 0.38 μM against VEGFR-2, 66, 40 nM against hCA IX and 7.6, 3.2 nM against hCA XII, respectively), comparing with sorafenib and SLC-0111 (IC 50  = 0.43 μM, 53 and 4.8 nM, respectively). Moreover, the docking simulation was assessed to supply better rationalization and gain insight into the binding affinity between the promising derivatives and their targeted enzymes that was used for further modification in the anticancer field., (© 2024. The Author(s).)

A new dimeric C-glycoside polyketide chrysomycin F ( 1 ), along with four new monomeric compounds, chrysomycins G ( 2 ), H ( 3 ), I ( 4 ), J ( 5 ), as well as three known analogues, chrysomycins A ( 6 ), B ( 7 ), and C ( 8 ), were isolated and characterised from a strain of Streptomyces sp. obtained from a sediment sample collected from the South China Sea. Their structures were determined by detailed spectroscopic analysis. Chrysomycin F contains two diastereomers, whose structures were further elucidated by a biomimetic [2 + 2] photodimerisation of chrysomycin A. Chrysomycins B and C showed potent anti-tuberculosis activity against both wild-type Mycobacterium tuberculosis and a number of clinically isolated MDR M. tuberculosis strains.

Lycibarbarspermidines are unusual phenolamide glycosides characterized by a dicaffeoylspermidine core with multiple glycosyl substitutions, and serve as a major class of bioactive ingredients in the wolfberry. So far, little is known about the enzymatic basis of the glycosylation of phenolamides including dicaffeoylspermidine. Here, we identify five lycibarbarspermidine glycosyltransferases, LbUGT1-5, which are the first phenolamide-type glycosyltransferases and catalyze regioselective glycosylation of dicaffeoylspermidines to form structurally diverse lycibarbarspermidines in wolfberry. Notably, LbUGT3 acts as a distinctive enzyme that catalyzes a tandem sugar transfer to the ortho-dihydroxy group on the caffeoyl moiety to form the unusual ortho-diglucosylated product, while LbUGT1 accurately discriminates caffeoyl and dihydrocaffeoyl groups to catalyze a site-selective sugar transfer. Crystal structure analysis of the complexes of LbUGT1 and LbUGT3 with UDP, combined with molecular dynamics simulations, revealed the structural basis of the difference in glycosylation selectivity between LbUGT1 and LbUGT3. Site-directed mutagenesis illuminates a conserved tyrosine residue (Y389 in LbUGT1 and Y390 in LbUGT3) in PSPG box that plays a crucial role in regulating the regioselectivity of LbUGT1 and LbUGT3. Our study thus sheds light on the enzymatic underpinnings of the chemical diversity of lycibarbarspermidines in wolfberry, and expands the repertoire of glycosyltransferases in nature., (© 2024. The Author(s).)

A chemical investigation of Anthriscus sylvestris roots led to the isolation and characterization of two new nitrogen-containing phenylpropanoids ( 1 - 2 ) and two new phenol glycosides ( 8 - 9 ), along with fifteen known analogues. Structure elucidation was based on HRESIMS, 1D and 2D NMR spectroscopy, and electronic circular dichroism (ECD). In addition, compounds 3 , 6 , 9 - 10 , 12 , and 17 exhibited inhibitory effects against the abnormal proliferation of pulmonary arterial smooth muscle cells with IC50 values ranging from 10.7 ± 0.6 to 57.1 ± 1.1 μM.

Six ionone glycosides ( 1 - 3 and 5 - 7 ), including three new ones, named capitsesqsides A-C ( 1 - 3 ), together with an eudesmane sesquiterpenoid glycoside ( 4 ) and three known triterpenoid saponins ( 8 - 10 ) were isolated from Rhododendron capitatum . The structures of these compounds were determined by extensive spectroscopic techniques (MS, UV, 1D-NMR, and 2D-NMR) and comparison with data reported in the literature. The absolute configurations were determined by comparison of the experimental and theoretically calculated ECD curves and LC-MS analyses after acid hydrolysis and derivatization. The anti-inflammatory activities of these compounds were evaluated in the LPS-induced RAW264.7 cells. Molecular docking demonstrated that 2 has a favorable affinity for NLRP3 and iNOS.

Staphylea , also called bladdernuts, is a genus of plants belonging to the family Staphyleaceae, widespread in tropical or temperate climates of America, Europe, and the Far East. Staphylea spp. produce bioactive metabolites with antioxidant properties, including polyphenols which have not been completely investigated for their phytotherapeutic potential, even though they have a long history of use for food. Here, we report the isolation of six flavonol glycosides from the hydroalcoholic extract of aerial parts of Staphylea pinnata L., collected in Italy, using a solid-phase extraction technique. They were identified using spectroscopic, spectrometric, and optical methods as three quercetin and three isorhamnetin glycosides. Among the flavonol glycosides isolated, isoquercetin and quercetin malonyl glucoside showed powerful antioxidant, antimicrobial, and wound healing promoting activity and thus are valuable as antiaging ingredients for cosmeceutical applications and for therapeutic applications in skin wound repair.

Reported herein is a new method for the direct synthesis of glycosyl chlorides from thioglycosides using sulfuryl chloride at rt. A variety of thioglycosides and thioimidates could be used as substrates. Both acid- and base-sensitive protecting groups were found compatible with these reaction conditions. Preliminary investigation of the reaction mechanism indicates chlorination of the leaving group at the anomeric sulfur as the key step of the reaction.

Thymine DNA glycosylase (TDG)-mediated excision of 5-formylcytosine and 5-carboxylcytosine (5-caC) is a critical step in active DNA demethylation. Herein, we employed a combined quantum mechanics/molecular mechanics approach to investigate the reaction mechanism of TDG-catalyzed N-glycosidic bond cleavage of 5-caC. The calculated results show that TDG-catalyzed 5-caC excision follows a concerted (S N 2) mechanism in which glycosidic bond dissociation is coupled with nucleophile attack. Protonation of the 5-caC anion contributes to the cleavage of the N-glycoside bond, in which the N3-protonated zwitterion and imino tautomers are more favorable than carboxyl-protonated amino tautomers. This is consistent with the experimental data. Furthermore, our results reveal that the configuration rearrangement process of the protonated 5-caC would lower the stability of the N-glycoside bond and substantially reduce the barrier height for the subsequent C1'-N1 bond cleavage. This should be attributed to the smaller electrostatic repulsion between the leaving base and the negative phosphate group as a result of the structural rearrangement.

Cassava extracts containing cyanogenic compounds demonstrate anticancer properties. The cyanogenic glucoside linamarin found abundantly in cassava can release hydrogen cyanide (HCN) upon hydrolysis, a potent cytotoxin. However, linamarin's hydrolysis mechanism by human enzymes is poorly delineated and constitutes a bottleneck for therapeutic development. This study aimed to investigate linamarin's hydrolysis mechanism by human β-glucosidase and identify structural derivatives with enhanced hydrolytic potential using density functional theory calculations. Results revealed α-anomeric derivatives as promising, with leaving group ability and steric bulk strongly governing hydrolysability. We identified several linamarin analogs with predicted rapid hydrolysis kinetics that may enable swift cytotoxic HCN release against cancer cells. This investigation enriches understanding of cyanogenic glycoside reactivity to facilitate their development as targeted antineoplastic agents. The identified derivatives set the groundwork for experimental evaluation of enhanced linamarin-inspired compounds as innovative cancer therapeutics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Bergenin, a rare C-glycoside of 4-O-methyl gallic acid with pharmacological properties of antitussive and expectorant, is widely used in clinics to treat chronic tracheitis in China. However, its low abundance in nature and structural specificity hampers the accessibility through traditional crop-based manufacturing or chemical synthesis. In the present work, we elucidate the biosynthetic pathway of bergenin in Ardisia japonica by identifying the highly regio- and/or stereoselective 2-C-glycosyltransferases and 4-O-methyltransferases. Then, in Escherichia coli, we reconstruct the de novo biosynthetic pathway of 4-O-methyl gallic acid 2-C-β-D-glycoside, which is the direct precursor of bergenin and is conveniently esterified into bergenin by in situ acid treatment. Moreover, further metabolic engineering improves the production of bergenin to 1.41 g L -1 in a 3-L bioreactor. Our work provides a foundation for sustainable supply of bergenin and alleviates its resource shortage via a synthetic biology approach., (© 2024. The Author(s).)

Glycosidic linkage analysis was conducted on the unfractionated polysaccharides in alcohol-insoluble residues (AIRs) prepared from six red seaweeds ( Gracilariopsis sp., Prionitis sp., Mastocarpus papillatus , Callophyllis sp., Mazzaella splendens , and Palmaria palmata ) using GC-MS/FID analysis of partially methylated alditol acetates (PMAAs). The cell walls of P. palmata primarily contained mixed-linkage xylans and small amounts of sulfated galactans and cellulose. In contrast, the unfractionated polysaccharides of the other five species were rich in galactans displaying diverse 3,6-anhydro-galactose and galactose linkages with varied sulfation patterns. Different levels of cellulose were also observed. This glycosidic linkage method offers advantages for cellulose analysis over traditional monosaccharide analysis that is known for underrepresenting glucose in crystalline cellulose. Relative linkage compositions calculated from GC-MS and GC-FID measurements showed that anhydro sugar linkages generated more responses in the latter detection method. This improved linkage workflow presents a useful tool for studying polysaccharide structural variations across red seaweed species. Furthermore, for the first time, relative linkage compositions from GC-MS and GC-FID measurements, along with normalized FID and total ion current (TIC) chromatograms without peak assignments, were analyzed using principal component analysis (PCA) as a proof-of-concept demonstration of the technique's potential to differentiate various red seaweed species.

A new tetramic acid glycoside, aurantoside L ( 1 ), was isolated from the sponge Siliquariaspongia japonica collected at Tsushima Is., Nagasaki Prefecture, Japan. The structure of aurantoside L ( 1 ) composed of a tetramic acid bearing a chlorinated polyene system and a trisaccharide part was elucidated using spectral analysis. Aurantoside L ( 1 ) showed anti-parasitic activity against L. amazonensis with an IC 50 value of 0.74 µM.

Inflammation is a pivotal factor in the development and advancement of conditions like NAFLD and asthma. Diet can affect several phases of inflammation and significantly influence multiple inflammatory disorders. Siraitia grosvenorii , a traditional Chinese edible and medicinal plant, is considered beneficial to health. Flavonoids can suppress inflammatory cytokines, which play a crucial role in regulating inflammation. In the present experiments, kaempferol 3- O - α -L-rhamnoside-7- O - β -D-xylosyl(1→2)- O - α -L-rhamnoside (SGPF) is a flavonoid glycoside that was first isolated from S . grosvenorii . A series of experimental investigations were carried out to investigate whether the flavonoid component has anti-inflammatory and hepatoprotective effects in this plant. The researchers showed that SGPF has a stronger modulation of protein expression in LPS-induced macrophages (MH-S) and OA-induced HepG2 cells. The drug was dose-dependent on cells, and in the TLR4/NF-κB/MyD88 pathway and Nrf2/HO-1 pathway, SGPF regulated all protein expression. SGPF has a clear anti-inflammatory and hepatoprotective function in inflammatory conditions.

This study accessed the potential antimalarial activity of triterpene glycoside of H. atra through targeting orotidine 5-monophosphate decarboxylase protein (PfOMPDC) in P. falciparum by molecular docking. Nine triterpene glycosides from H. atra extract modeled the structure by the Corina web server and interacted with PfOMPDC protein by using Hex 8.0.0. The docking results were visualized and analyzed by Discovery Studio version 21.1.1. 17-Hydroxyfuscocineroside B showed the lowest binding energy in PfOMPDC interaction, which was -1,098.13 kJ/mol. Holothurin A3, echinoside A, and fuscocineroside C showed low binding energy. Nine triterpene glycosides of H. atra performed interaction with PfOMPDC protein at the same region. Holothurin A1 posed interaction with PfOMPDC protein by 8 hydrogen bonds, 3 hydrophobic interactions, and 8 unfavorable bonds. Several residues were detected in the same active sites of other triterpene glycosides. Residue TYR111 was identified in all triterpene glycoside complexes, except holothurin A3 and calcigeroside B. In summary, the triterpene glycoside of H. atra is potentially a drug candidate for malaria therapeutic agents. In vitro and in vivo studies were required for further investigation., Competing Interests: No potential conflict of interest was reported by the authors., (Copyright © 2024 Prawesty Diah Utami et al.)

Five new biflorane-type diterpenoids, biofloranates E-I ( 1 - 5 ), and two new bicyclic diterpene glycosides, lemnaboursides H-I ( 6 - 7 ), along with the known lemnabourside, were isolated from the South China Sea soft coral Lemnalia bournei . Their chemical structures and stereochemistry were determined based on extensive spectroscopic methods, including time-dependent density functional theory (TDDFT) ECD calculations, as well as a comparison of them with the reported values. The antibacterial activities of the isolated compounds were evaluated against five pathogenic bacteria, and all of these diterpenes and diterpene glycosides showed antibacterial activities against Staphylococcus aureus and Bacillus subtilis , with MICs ranging from 4 to 64 µg/mL. In addition, these compounds did not exhibit noticeable cytotoxicities on A549, Hela, and HepG2 cancer cell lines, at 20 μM.

This study unveils an innovative method for synthesizing coumarin S -glycosides, employing original biocatalysts able to graft diverse carbohydrate structures onto 7-mercapto-4-methyl-coumarin in one-pot reactions. The fluorescence properties of the generated thio-derivatives were assessed, providing valuable insights into their potential applications in biological imaging or sensing. In addition, the synthesized compounds exhibited no cytotoxicity across various human cell lines. This research presents a promising avenue for the development of coumarin S -glycosides, paving the way for their application in diverse biomedical research areas.

Two disaccharides, methyl β-d-galactopyranosyl-(1→4)-α-d-glucopyranoside ( 1 ) and methyl β-d-galactopyranosyl-(1→4)-3-deoxy-α-d- ribo -hexopyranoside ( 3 ), were prepared with selective 13 C-enrichment to allow measurement of six trans- O -glycosidic J -couplings ( 2 J COC , 3 J COCH , and 3 J COCC ) in each compound. Density functional theory (DFT) was used to parameterize Karplus-like equations that relate these J -couplings to either ϕ or ψ . MA'AT analysis was applied to both linkages to determine mean values of ϕ and ψ in each disaccharide and their associated circular standard deviations (CSDs). Results show that deoxygenation at C3 of 1 has little effect on both the mean values and librational motions of the linkage torsion angles. This finding implies that, if inter-residue hydrogen bonding between O3H and O5' of 1 is present in aqueous solution and persistent, it plays little if any role in dictating preferred linkage conformation. Hydrogen bonding may lower the energy of the preferred linkage geometry but does not determine it to any appreciable extent. Aqueous 1-μs MD simulation supports this conclusion and also indicates greater conformational flexibility in deoxydisaccharide 3 in terms of sampling several, conformationally distinct, higher-energy conformers in solution. The populations of these latter conformers are low (3-14%) and could not be validated by MA'AT analysis. If the MD model is correct, however, C3 deoxygenation does enable conformational sampling over a wider range of ϕ / ψ values, but linkage conformation in the predominant conformer is essentially identical in both 1 and 3 .

Fourteen new 2-benzylbenzofuran O-glycosides (1-13, 15) and one new key precursor, diarylacetone (14) were isolated from the roots of Heterosmilax yunnanensis Gagnep, which all have characteristic 2,3,4-O-trisubstituted benzyl. Their structures were elucidated by 1D and 2D NMR, HRESIMS, UV and IR. The isolated compounds were assessed for their cardioprotective activities and compounds 1, 3 and 6 could significantly improve cardiomyocytes viability. Moreover, the mechanistic study revealed that these three compounds could significantly decrease intracellular ROS levels and maintain mitochondrial homeostasis upon hypoxia inducement. Consequently, 1, 3 and 6 might serve as potential lead compounds to prevent myocardial ischemia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

High-value chemicals and energy-related products can be produced from biomass. Biorefinery technology offers a sustainable and cost-effective method for this high-value conversion. β-glucosidase is one of the key enzymes in biorefinery processes, catalyzing the production of glucose from aryl-glycosides and cello-oligosaccharides via the hydrolysis of β-glycosidic bonds. Although β-glucosidase plays a critical catalytic role in the utilization of cellulosic biomass, its efficacy is often limited by substrate or product inhibitions, low thermostability, and/or insufficient catalytic activity. To provide a detailed overview of β-glucosidases and their benefits in certain desired applications, we collected and summarized extensive information from literature and public databases, covering β-glucosidases in different glycosidase hydrolase families and biological kingdoms. These β-glucosidases show differences in amino acid sequence, which are translated into varying degrees of the molecular properties critical in enzymatic applications. This review describes studies on the diversity of β-glucosidases related to the classification, catalytic mechanisms, key molecular characteristics, kinetics models, and applications, and highlights several β-glucosidases displaying high stability, activity, and resistance to glucose inhibition suitable for desired biotechnological applications., Competing Interests: Declaration of Competing Interest The authors indicate no potential conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Nymphoides peltata has been used as a medicinal herb in traditional medicines to treat strangury, polyuria, and swelling. The phytochemical investigation of the MeOH extract of N. peltata roots led to the isolation of three iridoid glycosides and three coumarin glycoside derivatives, which were characterized as menthiafolin ( 1 ), threoninosecologanin ( 2 ), callicoside C ( 3 ), and scopolin ( 4 ), as well as two undescribed peltatamarins A ( 5 ) and B ( 6 ). The chemical structures of the undescribed compounds were determined by analyzing their 1 dimensional (D) and 2D nuclear magnetic resonance (NMR) spectra and using high-resolution (HR)-electrospray ionization mass spectroscopy (ESI-MS), along with the chemical reaction of acid hydrolysis. The wound healing activities of the isolated compounds 1 - 6 were evaluated using a HaCaT cell scratch test. Among the isolates, scopolin ( 4 ) and peltatamarin A ( 5 ) promoted HaCaT cell migration over scratch wounds, and compound 5 was the most effective. Furthermore, compound 5 significantly promoted cell migration without adversely affecting cell proliferation, even when treated at a high dose (100 μM). Our results demonstrate that peltatamarin A ( 5 ), isolated from N. peltata roots, has the potential for wound healing effects.

The flavonoid glycoside apiin (apigenin 7- O -[β-D-apiosyl-(1→2)-β-D-glucoside]) is abundant in apiaceous and asteraceous plants, including celery and parsley. Although several enzymes involved in apiin biosynthesis have been identified in celery, many of the enzymes in parsley ( Petroselinum crispum ) have not been identified. In this study, we identified parsley genes encoding the glucosyltransferase, PcGlcT, and the apiosyltransferase, PcApiT, that catalyze the glycosylation steps of apiin biosynthesis. Their substrate specificities showed that they were involved in the biosynthesis of some flavonoid 7- O -apiosylglucosides, including apiin. The expression profiles of PcGlcT and PcApiT were closely correlated with the accumulation of flavonoid 7- O -apiosylglucosides in parsley organs and developmental stages. These findings support the idea that PcGlcT and PcApiT are involved in the biosynthesis of flavonoid 7- O -apiosylglucosides in parsley. The identification of these genes will elucidate the physiological significance of apiin and the development of apiin production methods.

Four new mono- and trisulfated triterpene penta- and tetraosides, djakonoviosides C 1 ( 1 ), D 1 ( 2 ), E 1 ( 3 ), and F 1 ( 4 ) were isolated from the Far Eastern sea cucumber Cucumaria djakonovi (Cucumariidae, Dendrochirotida), along with six known glycosides found earlier in other Cucumaria species. The structures of unreported compounds were established on the basis of extensive analysis of 1D and 2D NMR spectra as well as by HR-ESI-MS data. The set of compounds contains six different types of carbohydrate chains including two new ones. Thus, djakonovioside C 1 ( 1 ) is characterized by xylose as the second residue, that was a branchpoint in the pentasaccharide chain. Meanwhile, only quinovose and rarely glucose have been found earlier in pentasaccharide chains branched at C-2 of the second sugar unit. Djakonovioside E 1 ( 3 ) is characterized by a tetrasaccharide trisulfated chain, with glucose as the second residue. So, in the series of isolated glycosides, three types of sugars in the second position were presented: the most common, quinovose-in six compounds; glucose-in three substances; and the rare xylose-in one glycoside. The set of aglycones was composed of holostane- and non-holostane-type polycyclic systems; the latter comprised normal and reduced side chains. Noticeably, isokoreoside A ( 9 ), isolated from C. djakonovi , was a single glycoside having a 9(11)-double bond, indicating two oxidosqualenecyclases are operating in the process of the biosynthesis of aglycones. Some of the glycosides from C. djakonovi , which were characterized by pentasaccharide branched chains containing one to three sulfate groups, are chemotaxonomic features of the representatives of the genus Cucumaria . The assortment of sugar parts of Cucumaria's glycosides was broadened with previously undescribed penta- and tetrasaccharide moieties. The metabolic network of sugar parts and aglycones is constructed based on biogenetic relationships. The cytotoxic action of compounds 1 - 10 , isolated from C. djakonovi , against human breast cancer cell lines was investigated along with the hemolytic activity. Erythrocytes were, as usual, more sensitive to the membranolytic action of the glycosides than cancer cells. The triple-negative breast cancer MDA-MB-231 cell line was more vulnerable to the action of glycosides in comparison with the other tested cancer cells, while the MCF-7 cell line was less susceptible to cytotoxic action. Djakonovioside E 1 ( 3 ) demonstrated selective action against ER-positive MCF-7 and triple-negative MDA-MB-231 cell lines, while the toxic effect in relation to normal mammary epithelial cells (MCF-10A) was absent. Cucumarioside A 2 -5 ( 6 ) inhibited the formation and growth of colonies of cancer cells to 44% and tumor cell migration to 85% of the control. Quantitative structure-activity relationships (QSAR) were calculated on the basis of the correlational analysis of the physicochemical properties and structural features of the glycosidic molecules and their membranolytic activity. QSAR revealed the extremely complex nature of such relationships, but these calculations correlated well with the observed SAR.

The conformational study of saccharides and glycomimetics in solution is critical for a comprehensive understanding of their interactions with biological receptors and enabling the design of optimized glycomimetics. Here, we report a nuclear magnetic resonance (NMR) study centered on the conformational properties of the hydroxymethyl group and glycosidic bond of four series of aryl S -glucosides. We found that in acetyl-protected and free aryl S -β-glucosides, the rotational equilibrium around the C5-C6 bond (hydroxymethyl group) exhibits a linear dependence on the electronic properties of the aglycone, namely, as the aryl's substituent electron-withdrawing character increases, the dominance of the gg rotamer declines and the gt contribution rises. Likewise, the conformational equilibrium around the glycosidic C1-S bond also depends on the aglycone's electronic properties, where glucosides carrying electron-poor aglycones exhibit stiffer glycosidic bonds in comparison to their electron-rich counterparts. In the case of the α anomers, the aglycone's effect over the glycosidic bond conformation is like that observed on their β isomers; however, we observe no aglycone's influence over the hydroxymethyl group conformation in the α-glucosides.

To explore the complete biosynthesis process of flavonoid glycosides in safflower, specifically the key glycosyltransferase that might be involved, as well as to develop an efficient biocatalyst to synthesize flavonoid glycosides, a glycosyltransferase Ct UGT4, with flavonoid- O -glycosyltransferase activity, was identified in safflower. The fusion protein of Ct UGT4 was heterologously expressed in Escherichia coli , and the target protein was purified. The recombinant protein can catalyze quercetin to form quercetin-7- O -glucoside, and kaempferol to form kaempferol-3- O in vitro, and a series of flavones, flavonols, dihydroflavones, chalcones, and chalcone glycosides were used as substrates to generate new products. Ct UGT4 was expressed in the tobacco transient expression system, and the enzyme activity results showed that it could catalyze kaempferol to kaempferol-3- O -glucoside, and quercetin to quercetin-3- O -glucoside. After overexpressing CtUGT4 in safflower, the content of quercetin-3- O -rutinoside in the safflower florets increased significantly, and the content of quercetin-3- O -glucoside also tended to increase, which preliminarily confirmed the function of Ct UGT4 flavonoid- O -glycosyltransferase. This work demonstrated the flavonoid- O -glycosyltransferase function of safflower Ct UGT4 and showed differences in the affinity for different flavonoid substrates and the regioselectivity of catalytic sites in safflower, both in vivo and in vitro, providing clues for further research regarding the function of UGT genes, as well as new ideas for the cultivation engineering of the directional improvement of effective metabolites in safflower.

Biological degradation of natural product glycosides involves, alongside hydrolysis, β-elimination for glycosidic bond cleavage. Here, we discover an O-glycoside β-eliminase (OGE) from Agrobacterium tumefaciens that converts the C3-oxidized O-β-D-glucoside of phloretin (a plant-derived flavonoid) into the aglycone and the 2-hydroxy-3-keto-glycal elimination product. While unrelated in sequence, OGE is structurally homologous to, and shows effectively the same Mn 2+ active site as, the C-glycoside deglycosylating enzyme (CGE) from a human intestinal bacterium implicated in β-elimination of 3-keto C-β-D-glucosides. We show that CGE catalyzes β-elimination of 3-keto O- and C-β-D-glucosides while OGE is specific for the O-glycoside substrate. Substrate comparisons and mutagenesis for CGE uncover positioning of aglycone for protonic assistance by the enzyme as critically important for C-glycoside cleavage. Collectively, our study suggests convergent evolution of active site for β-elimination of 3-keto O-β-D-glucosides. C-Glycoside cleavage is a specialized feature of this active site which is elicited by substrate through finely tuned enzyme-aglycone interactions., (© 2023. The Author(s).)

Ligustrum robustum has been not only used as a heat-clearing and detoxicating functional tea (Ku-Ding-Cha) but also consumed as a hypotensive, anti-diabetic, and weight-reducing folk medicine. From the leaves of L. robustum , ten new monoterpenoid glycosides named ligurobustosides T 10 ( 1a ), T 11 ( 1b ), T 12 ( 2a ), T 13 ( 2b ), T 14 ( 3a ), T 15 ( 3b ), F 1 ( 4b ), T 16 ( 5a ), T 17 ( 5b ), and E 1 ( 6b ), together with five known ones ( 4a , 6a , 7 , 8a , 8b ), were separated and identified using the spectroscopic method and chemical method in this research. The results of biological tests exhibited that the fatty acid synthase (FAS) inhibitory action of compound 5 (IC 50 : 4.38 ± 0.11 μM) was as strong as orlistat (IC 50 : 4.46 ± 0.13 μM), a positive control; the α-glucosidase inhibitory actions of compounds 1 - 4 and 7 - 8 , and the α-amylase inhibitory actions of compounds 1 - 8 were medium; the ABTS radical scavenging capacities of compounds 1 - 3 and 5 - 8 (IC 50 : 6.27 ± 0.23 ~ 8.59 ± 0.09 μM) were stronger than l-(+)-ascorbic acid (IC 50 : 10.06 ± 0.19 μM) served as a positive control. This research offered a theoretical foundation for the leaves of L. robustum to prevent diabetes and its complications.

Investigation of the Vietnamese marine sponge Rhabdastrella globostellata led to the isolation of two new polar isomalabaricanes: rhabdastrellosides A ( 1 ) and B ( 2 ). Their structures and stereochemistry were elucidated with the application of 1D and 2D NMR, HRESIMS, and HRESIMS/MS methods, as well as chemical modifications and GC-MS analysis. Metabolites 1 and 2 are the first isomalabaricanes with non-oxidized cyclopentane ring in the tricyclic core system. Moreover, having a 3-O-disaccharide moiety in their structures, they increase a very rare group of isomalabaricane glycosides. We report here a weak cytotoxicity of 1 and 2 toward human neuroblastoma SH-SY5Y cells and normal rat H9c2 cardiomyocytes, as well as the cytoprotective activity of rhabdastrelloside B ( 2 ) at 1 µM evaluated using CoCl 2 -treated SH-SY5Y and H9c2 cells.

The Averrhoa carambola L. tree encompasses a myriad of phytochemicals contributing to its nutritional and health benefits. The current study aims at investigating the A. carambola L. the metabolite profile grown in tropical and temperate regions represented by fruit and stem, for the first time using UPLC/MS-based molecular networking and chemometrics. Asides, assessment of the immunostimulatory effect of ripe fruit and stem, was compared in relation to metabolite fingerprints. Eighty metabolites were identified, 8 of which are first-time to be reported including 3 dihydrochalcone-C-glycosides, 4 flavonoids, and one phenolic. Multivariate data analysis revealed dihydrochalcones as origin-discriminating metabolites between temperate and tropical grown fruits. Further, an in vivo immunomodulatory assay in a cyclosporine A-induced rat model revealed a potential immune-enhancing effect as manifested by down-regulation of inflammatory markers (IL-6, INF-γ, IL-1, TLR4, and ESR) concurrent with the up-regulation of CD4 level and the CD4/CD8 ratio. Moreover, both extracts suppressed elevation of liver and kidney functions in serum as well as reduction in oxidative stress with concurrent increased levels of T-protein, albumin, globulin, and A/G ratio. This study pinpoints differences in secondary metabolite profiles amongst A. carambola L. accessions from different origins and organ type and its immunomodulatory action mechanisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

1,4-naphthoquinones are the most widespread naphthoquinone compounds. Recently, many 1,4-naphthoquinone glycosides with different structural features have been obtained from both nature and synthesis, which has led to an increasing variety of naphthoquinone glycosides. In this paper, the structure variety and biological activity in recent 20 years are reviewed, and classified them according to the source and structure characteristics. Meanwhile the synthetic methods of O-, S-, C- and N-naphthoquinone glycosides and their structure activity relationships are also described. It was referred that the presence of polar groups of C2 and C5 and non-polar groups attached to C3 on the naphthoquinone ring are beneficial for their biological activities. It will provide more comprehensive literature resources for the future research of 1, 4-naphthoquinone glycosides and lay a theoretical foundation., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Xiaoxia Liang reports financial support was provided by National Nature Science Foundation of China and the Central Government Funds of Guiding Local Scientific and Technological Development for Sichuan Province., (Copyright © 2023 Elsevier Inc. All rights reserved.)