Structure Of Aglycone Research Articles

Interglycosidic C5–C6 rotamer distributions of alkyl O-rutinosides

The conformational study of carbohydrates is critical to understand the molecular recognition mechanisms underlying their biological functions. Moreover, the systematic study of their conformational patterns can unlock useful tools to design optimized glycomimetics and drug candidates. Using nuclear magnetic resonance, we studied the interglycosidic rotamer equilibria of ester-protected and deprotected alkyl O-rutinosides (α-L-Rha(1,6)β-D-GlcOR). In the protected series, the equilibrium about the C5–C6 bond distributes among the three possible rotamers gg, gt, and tg, being gt the predominant conformer. In these series, the flexibility about C5–C6 shows a marked dependency on the aglycone's structure, where the increase on the aglycone's volume leads to a progressive increment on the tg contributions at the expense of gt, with gg remaining practically constant along the series. The removal of the protective groups results in rutinosides displaying an equilibrium equally distributed between gg and gt with no tg contributions regardless of the aglycone's structure.

Sp2-Iminosugar azobenzene O-glycosides: Light-sensitive glycosidase inhibitors with unprecedented tunability and switching factors

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 sp2-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 103-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.

Fine-Scale Characterization of Plant Diterpene Glycosides Using Energy-Resolved Untargeted LC-MS/MS Metabolomics Analysis.

Plant diterpene glycosides are essential for diverse physiological processes. Comprehensive structural characterization proved to be a challenge due to variations in glycosylation patterns, diverse aglycone structures, and the absence of comprehensive reference databases. In this study, a method for fine-scale characterization was proposed based on energy-resolved (ER) untargeted LC-MS/MS metabolomics analysis using steviol glycosides as a demonstration. Energy-dependent fragmentation patterns were unveiled by a series of model compounds. Distinct glycosylation sites were discerned by leveraging varying fragmentation energies for the precursor ions. The sugar moiety linkage at C19OOH (R1) exhibited facile and intact cleavage at low collision energies, while the sugar moiety at C13-OH (R2) demonstrated consecutive cleavage with increasing energy. Aglycone ions exhibited a higher relative intensity at NCE 50, with relative intensities ranging from 95% to 100%. Subsequently, aglycone candidates, R1 sugar composition, and R2 sugar sequence were deduced through ER-MS/MS analysis. The developed method was applied to Stevia rebaudiana leaves. A total of 91 diterpene glycosides were unambiguously identified, including 16 steviol glycosides with novel acetylglycosylation patterns. This method offers a rapid alternative for glycan analysis and the structural differentiation of isomers. The developed method enhances the understanding of diterpene glycosides in plants, providing a reliable tool for the in-depth characterization of complex metabolite profiles.

Binding of Quercetin Derivatives toward G-Tetrads as Studied by the Survival Yield Method.

Recently, much interest has been devoted to finding effective G-quadruplex ligands, both of synthetic or natural origins, which may be of potential use in the field of cancer therapy. Among compounds of natural origin, a common flavonol quercetin has attracted notable attention. Yet, only a modest number of papers have been concerned with a comparison of quercetin conjugates binding to G-quadruplexes. In this study, we applied the survival yield (SY) method in order to compare the stability of G-tetrad complexes with quercetin and its conjugates, namely, 3-O-glycosides and O-methylated conjugates. According to the determined values of Ecomδ50, flavonol glycosides bind most effectively with G-tetrads, whereas, among flavonols, 3-O-methylquercetin makes the most effective bonds. Because the aglycone structure is of crucial importance for biological processes, 3-O-methylquercetin seems to be a suitable candidate for anticancer therapeutics, and the extracts from the plants, which contain high amounts of 3-O-methylquercetin or its glycosides, should be considered as interesting materials for preparation of pharmaceuticals or dietary supplements.

Investigating the initial steps of auricin biosynthesis using synthetic biology

Streptomyces lavendulae subsp. lavendulae CCM 3239 (formerly Streptomyces aureofaciens CCM 3239) contains a type II polyketide synthase (PKS) biosynthetic gene cluster (BGC) aur1 whose genes were highly similar to angucycline BGCs. However, its product auricin is structurally different from all known angucyclines. It contains a spiroketal pyranonaphthoquinone aglycone similar to griseusins and is modified with d-forosamine. Here, we describe the characterization of the initial steps in auricin biosynthesis using a synthetic-biology-based approach. We have created a plasmid system based on the strong kasOp* promoter, RBS and phage PhiBT1-based integration vector, where each gene in the artificial operon can be easily replaced by another gene using unique restriction sites surrounding each gene in the operon. The system was validated with the initial landomycin biosynthetic genes lanABCFDLE, leading to the production of rabelomycin after its integration into Streptomyces coelicolor M1146. However, the aur1DEFCGHA homologous genes from the auricin aur1 BGC failed to produce rabelomycin in this system. The cause of this failure was inactive aur1DE genes encoding ketosynthases α and β (KSα, KSβ). Their replacement with homologous aur2AB genes from the adjacent aur2 BGC resulted in rabelomycin production that was even higher after the insertion of two genes from the aur1 BGC, aur1L encoding 4-phosphopantetheinyl transferase (PPTase) and aur1M encoding malonyl-CoA:ACP transacylase (MCAT), suggesting that Aur1L PPTase is essential for the activation of the acyl carrier protein Aur1F. These results suggest an interesting communication of two BGCs, aur1 and aur2, in the biosynthesis of the initial structure of auricin aglycone.

Inhibiting Angiogenesis by Anti-Cancer Saponins: From Phytochemistry to Cellular Signaling Pathways

Saponins are one of the broadest classes of high-molecular-weight natural compounds, consisting mainly of a non-polar moiety with 27 to 30 carbons and a polar moiety containing sugars attached to the sapogenin structure. Saponins are found in more than 100 plant families as well as found in marine organisms. Saponins have several therapeutic effects, including their administration in the treatment of various cancers. These compounds also reveal noteworthy anti-angiogenesis effects as one of the critical strategies for inhibiting cancer growth and metastasis. In this study, a comprehensive review is performed on electronic databases, including PubMed, Scopus, ScienceDirect, and ProQuest. Accordingly, the structural characteristics of triterpenoid/steroid saponins and their anti-cancer effects were highlighted, focusing on their anti-angiogenic effects and related mechanisms. Consequently, the anti-angiogenic effects of saponins, inhibiting the expression of genes related to vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1-α (HIF-1α) are two main anti-angiogenic mechanisms of triterpenoid and steroidal saponins. The inhibition of inflammatory signaling pathways that stimulate angiogenesis, such as pro-inflammatory cytokines, mitogen-activated protein kinase (MAPKs), and phosphoinositide 3-kinases/protein kinase B (PI3K/Akt), are other anti-angiogenic mechanisms of saponins. Furthermore, the anti-angiogenic and anti-cancer activity of saponins was closely related to the binding site of the sugar moiety, the type and number of their monosaccharide units, as well as the presence of some functional groups in their aglycone structure. Therefore, saponins are suitable candidates for cancer treatment by inhibiting angiogenesis, for which extensive pre-clinical and comprehensive clinical trial studies are recommended.

Replacement of Acetonitrile with Ethanol in the Determination of Anthocyanins by Reversed-Phase High-Performance Liquid Chromatography

It was found experimentally that the replacement of acetonitrile with ethanol upon the acidification of the mobile phase with phosphoric acid is an effective version for replacing acetonitrile. At that, the order of elution of glycosides of the same type of the five main anthocyanidins (delphinidin, cyanidin, petunidin, peonidin, and malvidin) does not change in eluents convenient for analysis, and the range of retention times for a complete set of such anthocyanins becomes noticeably narrower in going from acetonitrile to ethanol. To determine the effect of aglycone structure on the retention of derivatives of the same anthocyanidin (cyanidin), a mixture of six glycosides was used: one monoglycoside (3-glucoside), two 3-diglycosides (sophoroside and sambubioside), and two 3-triglycosides (2"-glucosylrutinoside and 2"-xylosylrutinoside). This mixture is a real set of anthocyanins, requiring the careful selection of the mobile phase for separating all components. In this work, based on an analysis of separation maps, the composition of a mobile phase based on ethanol is determined that ensures the achievement of the effective separation of these anthocyanins.

Characterization of ginsenoside structural isomers from mixtures using in situ methylation with direct analysis in real-time ionization tandem mass spectrometry

Characterization of structural isomers of bioactive molecules is important for recognizing their functions, but it has been challenging due to their highly similar structures. As the main bioactive constituents of Panax ginseng, ginsenosides have different structural isomers attributed to the aglycone structure and glycosylation sites as well as stereochemistry of sugar groups attached. This work demonstrated a simple and robust in situ methylation reaction with tetramethylammonium hydroxide (TMAH) using ambient ionization source of direct analysis in real time (DART) to characterize saponin structural isomers. The DART ion source provides favorable conditions to methylate hydroxyl groups of ginsenoside instantaneously with TMAH, and it can ionize the methylated products at the same time. Methylated ginsenoside stereoisomers even with subtle structure differences generated very different mass signals from full-scan MS and tandem MS. High-resolution mass spectrometry aided the assignment of molecular structures of the various precursor and fragment ions from different ginsenosides, which provided structural information for both the aglycone skeleton and the sugar moieties in ginsenosides. The presented method was successfully used for the identification of ginsenosides in Panax ginseng, and saponin isomers were characterized without the need for chromatographic separation and/or tedious offline sample pretreatment.

The Isolation, Structure Elucidation and Bioactivity Study of Chilensosides A, A1, B, C, and D, Holostane Triterpene Di-, Tri- and Tetrasulfated Pentaosides from the Sea Cucumber Paracaudina chilensis (Caudinidae, Molpadida).

Five new triterpene (4,4,14-trimethylsterol) di-, tri- and tetrasulfated pentaosides, chilensosides A (1), A1 (2), B (3), C (4), and D (5) were isolated from the Far-Eastern sea cucumber Paracaudina chilensis. The structures were established on the basis of extensive analysis of 1D and 2D NMR spectra and confirmed by HR-ESI-MS data. The structural variability of the glycosides concerned the pentasaccharide chains. Their architecture was characterized by the upper semi-chain consisting of three sugar units and the bottom semi-chain of two sugars. Carbohydrate chains of compounds 2-5 differed in the quantity and positions of sulfate groups. The interesting structural features of the glycosides were: the presence of two sulfate groups at C-4 and C-6 of the same glucose residue in the upper semi-chain of 1, 2, 4, and 5 and the sulfation at C-3 of terminal glucose residue in the bottom semi-chain of 4 that makes its further elongation impossible. Chilensoside D (5) was the sixth tetrasulfated glycoside found in sea cucumbers. The architecture of the sugar chains of chilensosides A-D (1-5), the positions of sulfation, the quantity of sulfate groups, as well as the aglycone structures, demonstrate their similarity to the glycosides of the representatives of the order Dendrochirotida, confirming the phylogenetic closeness of the orders Molpadida and Dendrochirotida. The cytotoxic activities of the compounds 1-5 against human erythrocytes and some cancer cell lines are presented. Disulfated chilensosides A1 (2) and B (3) and trisulfated chilensoside C (4) showed significant cytotoxic activity against human cancer cells.

Insights into the Activation of Alkyne-Installed Glycosyl Donors with Dual Acidic Metal Catalysts: Reaction Pathway, Influencing Factors, and Enlightenment for Glycosylation.

The activation of alkyne-installed glycosyl donors with dual acidic metal catalysts were studied. Lewis and/or π acidity-activated pathways were observed for alkynyl carbonate-, ester-, and ether-type donors, and π acidity-promoted reaction mode afforded higher efficiency and yields. The activation mode for a certain metal catalyst is determined by the nature of catalysts itself, protecting groups on sugar rings, type of sugars, and structure of aglycones. The discovery gives us valuable insights into the glycosylation of alkyne-containing donors.

Genetic and Molecular Characterization of a New EMS-Induced Mutant without the Third Glucose Moiety at the C-3 Sugar Chain of Saponin in Glycine max (L.) Merr.

Saponin, a secondary metabolite, is produced by various plant species, including soybean (Glycine max (L.) Merr.). Soybeans synthesize triterpenoid saponins, which are classified by their aglycone structure and sugar chain composition. Here, we characterized an ethyl methanesulfonate-induced mutant, PE1539, without saponin and with a glucose moiety at the third position of the C-3 sugar chain. The saponin phenotype of PE1539 is described by the accumulation of Ab-γg saponin and deficiency of Ab-αg saponin and DDMP-αg saponin, similar to a previously reported sg-3 mutant in soybean. Genetic analysis showed that the saponin phenotype of PE1539 is controlled by a recessive mutation. We mapped the gene responsible for the phenotype of PE1539 and the mapped region included Sg-3 (Glyma.10G104700). Further analysis of Sg-3 in PE1539 using DNA sequencing revealed a single-nucleotide substitution in the exon (G804A), resulting in a premature stop codon; thus, PE1539 produced a PSPG box-truncated protein. Saponin phenotype analysis of the F2 population—from a cross between wild-type Uram and PE1539—showed that the phenotype of saponin was cosegregated with the genotype of Sg-3. Quantitative real-time PCR showed reduced expression of Sg-3 in PE1539 cells. Together, our data indicate that the saponin phenotype of PE1539 results from a mutation in Sg-3.

Inhibition of Dipeptidyl Peptidase-4 by Flavonoids: Structure-Activity Relationship, Kinetics and Interaction Mechanism.

With the aim to establish a structure-inhibitory activity relationship of flavonoids against dipeptidyl peptidase-4 (DPP-4) and elucidate the interaction mechanisms between them, a pannel of 70 structurally diverse flavonoids was used to evaluate their inhibitory activities against DPP-4, among which myricetin, hyperoside, narcissoside, cyanidin 3-O-glucoside, and isoliquiritigenin showed higher inhibitory activities in a concentration-dependent manner. Structure-activity relationship analysis revealed that introducing hydroxyl groups to C3', C4', and C6 of the flavonoid structure was beneficial to improving the inhibitory efficacy against DPP-4, whereas the hydroxylation at position 3 of ring C in the flavonoid structure was unfavorable for the inhibition. Besides, the methylation of the hydroxyl groups at C3', C4', and C7 of the flavonoid structure tended to lower the inhibitory activity against DPP-4, and the 2,3-double bond and 4-carbonyl group on ring C of the flavonoid structure was essential for the inhibition. Glycosylation affected the inhibitory activity diversely, depending on the structure of flavonoid aglycone, type of glycoside, as well as the position of substitution. Inhibition kinetic analysis suggested that myricetin reversibly inhibited DPP-4 in a non-competitive mode, whereas hyperoside, narcissoside, cyanidin 3-O-glucoside, and isoliquiritigenin all reversibly inhibited DPP-4 in a mixed type. Moreover, the fluorescence quenching analysis indicated that all the five flavonoid compounds could effectively quench the intrinsic fluorescence of DPP-4 by spontaneously binding with it to form an unstable complex. Hydrogen bonds and van der Waals were the predominant forces to maintain the complex of myricetin with DPP-4, and electrostatic forces might play an important role in stabilizing the complexes of the remaining four flavonoids with DPP-4. The binding of the tested flavonoids to DPP-4 could also induce the conformation change of DPP-4 and thus led to inhibition on the enzyme. Molecular docking simulation further ascertained the binding interactions between DPP-4 and the selected five flavonoids, among which hyperoside, narcissoside, cyaniding 3-O-glucoside, and isoliquiritigenin inserted into the active site cavity of DPP-4 and interacted with the key amino acid residues of the active site, whereas the binding site of myricetin was located in a minor cavity close to the active pockets of DPP-4.

Characterization of Triterpene Saponin Glycyrrhizin Transport by Glycyrrhiza glabra.

Glycyrrhizin (GL), a triterpene compound produced by Glycyrrhiza species, is a crucial pharmacologically active component of crude drugs. In contrast to the biosynthesis of GL in plants, little is known about GL transport and accumulation in plants. The transport mechanism of GL was characterized using cultured cells of Glycyrrhiza glabra. Cultured cells of G. glabra efficiently incorporated exogenously supplied GL. Proton pump inhibitors, such as probenecid and niflumic acid, as well as a protonophore (carbonylcyanide m-chlorophenylhydrazone), markedly inhibited GL uptake by cultured cells, whereas vanadate exhibited a moderate inhibition. Furthermore, GL transport by G. glabra tonoplast vesicles is dependent not on a H+-electrochemical gradient but MgATP and is markedly inhibited by vanadate. These results suggest that GL uptake by cultured cells is mediated by a H+-symporter in the plasma membrane and an ATP-binding cassette transporter, which has high specificity for the aglycone structure of GL on the tonoplast.

Identification and quantitative analysis of anthocyanins composition and their stability from different strains of Hibiscus syriacus L. flowers

Hibiscus syriacus flower has high ornamental, edible and medicinal value. The pigments in the H. syriacus flower always tend to fade during food processing. To clarify composition and stability of the pigments, qualitative and quantitative analyses of anthocyanins in H. syriacus flower were performed by LC-ESI-QTOF-MS, and the total anthocyanins with variations in presence of some factors were determined by UV-Vis and HPLC. The results showed that the anthocyanins contained in the four strains of H. syriacus were HSR>HSPU>HSP>HSW. Among the 40 color-related components identified in H. syriacus flowers, the anthocyanin aglycone structures involved included cyanidin, delphinidin, procyanidin, peonidin, pelargonidin, petunidin, malvidin, and dihydroflavonoids, but the depth of the flower color was mainly related to the number of functional groups on B-ring of skeleton. In the temperature range of 4–65 ℃, higher temperatures had a significant color-enhancing effect on the anthocyanins. Light significantly promoted the degradation of anthocyanins, while acidic conditions were conducive to the stability of the anthocyanins in H. syriacus flowers. Metal-ions of Cu2+, Mg2+ and Al3+, ascorbic acid, oxidant and reducing agent can reduce the stability of anthocyanins. The research data provides scientific guidance and foundation for the breeding, resource utilization and edible development of H. syriacus flower.

Structure-Activity Relationships of Holothuroid's Triterpene Glycosides and Some In Silico Insights Obtained by Molecular Dynamics Study on the Mechanisms of Their Membranolytic Action.

The article describes the structure-activity relationships (SAR) for a broad series of sea cucumber glycosides on different tumor cell lines and erythrocytes, and an in silico modulation of the interaction of selected glycosides from the sea cucumber Eupentacta fraudatrix with model erythrocyte membranes using full-atom molecular dynamics (MD) simulations. The in silico approach revealed that the glycosides bound to the membrane surface mainly through hydrophobic interactions and hydrogen bonds. The mode of such interactions depends on the aglycone structure, including the side chain structural peculiarities, and varies to a great extent. Two different mechanisms of glycoside/membrane interactions were discovered. The first one was realized through the pore formation (by cucumariosides A1 (40) and A8 (44)), preceded by bonding of the glycosides with membrane sphingomyelin, phospholipids, and cholesterol. Noncovalent intermolecular interactions inside multimolecular membrane complexes and their stoichiometry differed for 40 and 44. The second mechanism was realized by cucumarioside A2 (59) through the formation of phospholipid and cholesterol clusters in the outer and inner membrane leaflets, correspondingly. Noticeably, the glycoside/phospholipid interactions were more favorable compared to the glycoside/cholesterol interactions, but the glycoside possessed an agglomerating action towards the cholesterol molecules from the inner membrane leaflet. In silico simulations of the interactions of cucumarioside A7 (45) with model membrane demonstrated only slight interactions with phospholipid polar heads and the absence of glycoside/cholesterol interactions. This fact correlated well with very low experimental hemolytic activity of this substance. The observed peculiarities of membranotropic action are in good agreement with the corresponding experimental data on hemolytic activity of the investigated compounds in vitro.

Isopropyl 3-deoxy-α-D-ribo-hexopyranoside (isopropyl 3-deoxy-α-D-glucopyranoside): evaluating trends in structural parameters.

Isopropyl 3-deoxy-α-D-ribo-hexopyranoside (isopropyl 3-deoxy-α-D-glucopyranoside), C9H18O5, (I), crystallizes from a methanol-ethyl acetate solvent mixture at room temperature in a 4C1 chair conformation that is slightly distorted towards the C5SC1 twist-boat form. A comparison of the structural parameters in (I), methyl α-D-glucopyranoside, (II), α-D-glucopyranosyl-(1→4)-D-glucitol (maltitol), (III), and 3-deoxy-α-D-ribo-hexopyranose (3-deoxy-α-D-glucopyranose), (IV), shows that most endocyclic and exocyclic bond lengths, valence bond angles and torsion angles in the aldohexopyranosyl rings are more affected by anomeric configuration, aglycone structure and/or the conformation of exocyclic substituents, such as hydroxymethyl groups, than by monodeoxygenation at C3. The structural effects observed in the crystal structures of (I)-(IV) were confirmed though density functional theory (DFT) calculations in computed structures (I)c-(IV)c. Exocyclic hydroxymethyl groups adopt the gauche-gauche (gg) conformation (H5 anti to O6) in (I) and (III), and the gauche-trans (gt) conformation (C4 anti to O6) in (II) and (IV). The O-glycoside linkage conformations in (I) and (III) resemble those observed in disaccharides containing β-(1→4) linkages.

Quantum-Chemical Calculations for the Electronic Absorption Spectra of Certain Anthocyanidins

Semi-empirical PM3 calculations are made for the electronic absorption spectra of colored forms of nonmethylated anthocyanidins (aurantinidin, pelargonidin, cyanidin, and delphinidin). The position of the absorption band peak is shown to depend on the orientation of hydroxyl groups in the aglycone structure. The observed tendency toward a bathochromic shift after ОН groups are added to the ring generally corresponds to experimental data. The results for the uncharged quinonoid forms of pelargonidin (a hypsochromic shift of absorption bands) do not in this case agree with the prevailing opinion of specialists about the bathochromic shift. While this opinion is confirmed by DFT calculations, there are still no reliable experimental data on their validity. The formation of single-charged (negatively) quinonoid structures is clearly the reason for the bathochromic shift of absorption bands, which is consistent with the experimental data. When the charge multiplicity increases (to −2), a hypsochromic shift of absorption bands to the experimentally observed yellow color of anthocyanins in alkaline solutions is again predicted.

The Influence of Anomeric Configuration and Aglycone Structure on the Outcome of Acid‐Promoted Ring Contraction in 2,3‐Di‐O‐Silylated S‐Galactopyranosides

AbstractAcid‐promoted rearrangement of a series of 1‐thio‐α/β‐d‐galactopyranosides with bulky triisopropylsilyl (TIPS) or tert‐butyldiphenylsilyl (TBDPS) groups at both O‐2 and O‐3 and bearing various substituents at the S atom in anomeric position leading to ring contraction has been studied. The reaction rates of pyranose ring contraction in S‐galactopyranosides were found to be strongly influenced by anomeric configuration and aglycone structure. Ethyl 1‐thio‐β‐d‐galactopyranosides underwent ring contraction faster than ethyl 1‐thio‐α‐d‐thiogalactopyranosides. 1‐Thio‐β‐d‐galactopyranosides with TIPS groups bearing electron‐donating 5‐tert‐butyl‐2‐methylphenyl group in aglycone could be involved into rearrangement to furanosides under milder acidic conditions (aq TFA in CH2Cl2) than the corresponding 1‐thio‐β‐d‐galactopyranosides with phenyl or 4‐chlorophenyl groups in aglycone (anhydrous TFA in CH2Cl2). On the contrary, 1‐thio‐β‐d‐thiogalactopyranoside bearing electron‐withdrawing 4‐nitrophenyl group in aglycone did not undergo ring contraction under identical conditions.

Rapid analysis and identification of dianthrone glycosides in Polygoni Multiflori Caulis based on enrichment of macroporous absorbent resin and UPLC-Q-TOF-MS/MS.

Polygoni Multiflori Caulis (PMC) has been used as a traditional Chinese medicine for a long time in China. However, hepatotoxic events of PMC have been reported in recent years, but the potential toxic compounds have remained unclear. Dianthrones as the secondary plant metabolites were revealed to potential hepatotoxicity in a previous study. However, no reports focused on dianthrones in PMC. In the quest for exploring potential hepatotoxic compounds in PMC, the aim of this work was to undertake a comprehensive characterisation of dianthrones in PMC. A simple and effective macroporous absorbent resin column chromatography method was established in this study to enrich the minor dianthrones from PMC extracts. Exploration and characterisation of dianthrones in PMC was conducted by an ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS) method and information dependent acquisition (IDA) mode. The aglycones of dianthrone glycosides were further verified by acid hydrolysis method. Seventy-two dianthrone glycosides and their five aglycones were discovered and tentatively characterised in PMC for the first time, of which 29 dianthrones were identified as potential new compounds. Dianthrone glycosides could be classified into three types according to their aglycone structures, and their fragmentation pathway rules and diagnosed ions were also summarised comprehensively. This was the first comprehensive investigation on dianthrones in PMC. The result would help to fully understand the phytochemical constituents and toxic components in PMC, and highlight the need for further toxicological investigations of the dianthrones in PMC due to their potential hepatotoxicity correlation.

Grincamycins P-T: Rearranged Angucyclines from the Marine Sediment-Derived Streptomyces sp. CNZ-748 Inhibit Cell Lines of the Rare Cancer Pseudomyxoma Peritonei.

While marine natural products have been investigated for anticancer drug discovery, they are barely screened against rare cancers. Thus, in our effort to discover potential drug leads against the rare cancer pseudomyxoma peritonei (PMP), which currently lacks effective drug treatments, we screened extracts of marine actinomycete bacteria against the PMP cell line ABX023-1. This effort led to the isolation of nine rearranged angucyclines from Streptomyces sp. CNZ-748, including five new analogues, namely, grincamycins P-T (1-5). The chemical structures of these compounds were unambiguously established based on spectroscopic and chemical analyses. Particularly, grincamycin R (3) possesses an S-containing α-l-methylthio-aculose residue, which was discovered in nature for the first time. All of the isolated compounds were evaluated against four PMP cell lines and some exhibited low micromolar inhibitory activities. To identify a candidate biosynthetic gene cluster (BGC) encoding the grincamycins, we sequenced the genome of the producing strain, Streptomyces sp. CNZ-748, and compared the BGCs detected with those linked to the production of angucyclines with different aglycon structures.