Discovery of anti-neuroinflammatory agents from 1,4,5,6-tetrahydrobenzo[2,3]oxepino[4,5-d]pyrimidin-2-amine derivatives by regulating microglia polarization.

Neuroinflammation mediated by microglia activation leads to various neurodegenerative and neurological disorders. In order to develop more and better options for this disorders, a series of 3,4-dihydrobenzo[b]oxepin-5(2H)-one derivatives (BZPs, 6-19) and novel 1,4,5,6-tetrahydrobenzo[2,3]oxepino[4,5-d]pyrimidin-2-amine derivatives (BPMs, 20-33) were synthesized and screened the anti-neuroinflamamtion effects. 3,5-bis-trifluoromethylphenyl-substituted BPM 29 showed more potent anti-neuroinflammatory activity and no toxicity to BV2 microglia cells in vitro. 29 significantly reduced the number of M1 phenotype of microglia cells, but significantly increased the number of M2 phenotype of microglia cells in lipopolysaccharide (LPS)-induced BV2 microglia cells. 29 significantly reduced the secretion of inflammatory cytokines (IL-18, IL-1ß, TNF-α), but increased the secretion of anti-inflammatory cytokines (IL-10) from LPS-induced BV2 microglia cells. Also, 29 inhibited the NOD-like receptor NLRP3 inflammasome formation, and down-regulated the expression of M2 isoform of pyruvate kinase in LPS-induced BV2 microglia cells. In vivo, 29 reduced the neuroinflammation in cuprizone-induced inflammatory and demyelinating mice by reducing the expression of inducible nitric-oxide synthase, but increased the expression of CD206. Taken together, 29 might be a prospective anti-neuroinflammatory compound for neuroinflammatory and demyelinating disease by alleviating microglia activation.

Design, synthesis and anti-Chikungunya virus activity of lomerizine derivatives.

Chikungunya fever is an acute infectious disease caused by Chikungunya virus (CHIKV) and transmitted by Aedes mosquito. It is characterized by fever, rash and arthralgia with no effective drugs. Lomerizine (Lom) is a new generation calcium antagonist, which is mainly used in the treatment of migraine. Certain antiviral function of Lom was shown by some research. In our study, a series of new derivatives of Lom were designed and synthesized, and their in-vitro anti-CHIKV activity was tested. The results showed that Lom and its derivatives had potent anti-CHIKV activity and low cytotoxicity. Among them, compounds B1 and B7 showed most potent antiviral activity. Besides, structure-activity relationships, in-silico ADMET properties were also analyzed. Molecular docking study was performed to rationalize the SAR and analyze the possible binding modes between B1 and amino acid residues in the active site of nsP3 protein to enhance the understanding of their action as antiviral agents. These finding provides research basis for the design and synthesis of effective anti-CHIKV drugs with Lom as the lead compound.

Anti-inflammatory activity of fluorine-substituted benzo[h]quinazoline-2-amine derivatives as NF-κB inhibitors.

Excessive inflammation can cause loss of tissue or organ function, leading to a number of chronic diseases and sometimes even death. Traditional treatment strategies for inflammation have mainly involved steroidal and non-steroidal anti-inflammatory drugs, but both have increasingly prominent side effects. Nuclear factor kappa B (NF-κB) inhibitors with anti-inflammatory properties and low toxicity are a new therapeutic strategy for the treatment of inflammatory diseases. To obtain novel NF-κB inhibitors, a series of 3,4-dihydronaphthalen-1(2H)-one derivatives (DHNs 6a-s), 1,4,5,6-tetrahydrobenzo[h]quinazolin-2-amine derivatives (BQAs 7a-c) and 5,6-dihydrobenzo[h]quinazolin-2-amine derivatives (BQAs 8a-p) were designed and synthesized, and characterized by NMR and HRMS. By evaluating toxicity and anti-inflammatory properties, fluorine-substituted 8c showed more potential anti-inflammatory activity and lower toxicity. 8c significantly reduced the phosphorylation of IκBα and p65, thereby inhibiting the NF-κB signaling pathway. In addition, 8c markedly decreased reactive oxygen species (ROS) production and downregulated the expression of NOD-like receptor pyrin domain-containing protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC) and cysteine aspartate protein hydrolase-1 (caspase-1). Therefore, compound 8c is expected to be a candidate compound for NF-κB inhibition and deserves further research and development.

Research Progress of Duodenal-Jejunal Bypass Liner in the Treatment of Obesity and Type 2 Diabetes Mellitus.

With the development of economy and improvement of people's living standards, the incidence of obesity and type 2 diabetes mellitus (T2DM) has increased significantly and obesity has also become one of the most important risk factors of T2DM. In light of these trends, there have been many ways to take effect in losing weight. However, they also have corresponding deficiencies including inapparent curative effect, complex and incomplete reversible procedures and severe complications. Duodenal-Jejunal Bypass Liner (DJBL), which mimics Roux-en-Y gastric bypass (RYGB), is proved to play a key role in weight loss and control of T2DM. DJBL is reversible, less invasive and is more suitable for the treatment of obesity and T2DM, which is associated with multiple mechanisms, including incretin effect, gastric emptying mechanism, bile acid regulation, intestinal microbiota, inflammatory reaction mechanism and neural mechanism. In our review, we aimed to elaborate DJBL's clinical efficacy, safety and mechanisms in detail.

Single-cell transcriptomes from turtle livers reveal sensitivity of hepatic immune cells to bacteria-infection.

The liver is important in the synthesis, metabolism and storage of nutrients, detoxification and immune response of the body, and the liver immune response against exogenous pathogens from the intestinal tract plays a key role in the immune activities. However, the cellular composition of the liver immune atlas remains sparsely studied in reptiles. We used single-cell RNA sequencing to identify the cellular profile of the liver of the Chinese soft-shelled turtle (Pelodiscus sinensis). We obtained the transcriptional landscape based on 9938 cells from the fractionation of fresh hepatic tissues from two individuals, uninfected and infected with bacteria (Aeromonas hydrophila). We identified seven hepatic immune cell subsets, including plasma, erythroid, T/NK, B, endothelial, dendritic and Kupffer cells. Bacteria-infection altered the number of liver immune cells, as revealed by the fact that the infected turtle had more plasma, endothelial and Kupffer cells and fewer T/NK, dendritic and erythroid cells than did the uninfected turtle. Our study is the first to provide a comprehensive view of the hepatic immune landscape of P. sinensis at the single-cell resolution that outlines the characteristics of immune cells in the turtle liver and provides a liver transcriptome baseline for turtle immunology.

Synthesis, biological evaluation and molecular docking studies of novel diosgenin derivatives as anti-inflammatory agents.

Thirty-two novel DG F-spiroacetal ring-opening derivatives, including 24 acetylated derivatives and 8 nitrogenous derivatives, were designed and synthesized from diosgenin (DG). The cytotoxicity of the novel derivatives was evaluated by MTT assay, except for compounds 4a, 4e, 4i, 4 l, 5a and 5 h, which were potentially cytotoxic to RAW264.7 cells, all the other derivatives had no significant cytotoxicity. The NO release inhibitory activities of novel derivatives were screened by Griess method. The results showed that the anti-inflammatory activity of the DG acetylated derivatives was stronger than the nitrogenous derivatives, and 4a-4 m containing acetyl groups at the 3-position may have better anti-inflammatory effects than 5a-5 k containing free hydroxyl groups. In ELISA assay, compound 4 m exhibited potent anti-inflammatory activity by inhibiting the production of NO in RAW264.7 cells activated by LPS with IC50 values 0.449 ± 0.050 µM. The results of docking experiments showed that 4 m has a good affinity for p65 protein.

Anti-neuroinflammatory effects of novel 5,6-dihydrobenzo[h]quinazolin-2-amine derivatives in lipopolysaccharide-stimulated BV2 microglial cells.

Neuroinflammation is an intricate process that is associated with both normal and pathological conditions. Microglia-mediated neuroinflammation is known to lead to various neurodegenerative and neurological disorders. A series of 3,4-dihydronaphthalen-1(2H)-one derivatives (1-15) and novel 5,6-dihydrobenzo[h]quinazolin-2-amine derivatives (16-30) were synthesized and characterized by various analytical methods, such as NMR and HRMS. All compounds were evaluated for toxicity, screened for their anti-neuroinflammatory properties, and investigated for the potential molecular mechanism of lipopolysaccharide (LPS) induction in BV2 microglia. Structure activity relationship analysis showed that compound 17 substituted by the 7-fluorine atom on the A-ring and the 3-methoxy on the D-ring had more potential anti-neuroinflammatory activity by inhibiting the secretion of cytokines TNF-α and IL-6. The results of western blotting assay showed that 17 significantly blocked the activation and phosphorylation of IκBα, significantly reduce the expression of NLRP3 inflammatory vesicle-associated proteins, and thus inhibit the activation of NF-κB pathway. Thus, compound 17 was demonstrated to be an excellent potential therapeutic agent for the treatment of neuroinflammation-related diseases.

Discovery of anti-hepatoma agents from 1,4,5,6,7,8-hexahydropyrido[4,3-d]pyrimidine by inhibiting PI3K/AKT/NF-κB pathway activation.

In order to obtain new anti-hepatoma drugs with low toxicity, some 1,4,5,6,7,8-hexahydropyrido[4,3-d]pyrimidines (PPMs, 4a-t) were synthesized in this study. Many of them showed significant anti-hepatoma effects against HCC cells and low toxicity toward HHL-5 cells. Combined with their anti-hepatoma activity and toxicity, 4-CF3-substituted 4k was selected as an effective lead compound. Preliminary mechanistic studies revealed that 4k could up-regulate the expression levels of Bax and caspase-3 proteins, down-regulate the expression levels of Bcl-2 protein, promote significant apoptosis of HepG2, and block cells in G2-M phase to prevent cells from completing mitosis. Also, 4k could significantly inhibit the activation of PI3K/AKT/NF-κB pathway by blocking the phosphorylation of PI3K, AKT, NF-κB/p65 and IFN-γ-induced nuclear transport. Docking analysis showed that 4k could reasonably bind to the active sites of Bcl-2, NF-κB/p65, PI3K and AKT. This result suggested that 4k could be used as a new type of NF-κB inhibitor, which provides a scientific basis for further research into the treatment of hepatoma.

Synthesis and In Vitro anti-HCV and Antitumor Evaluation of Schisandronic Acid Derivatives.

BACKGROUND: Schisandronic acid (SA), a triterpenoid from fruits of Schisandra sphenanthera, inhibited pan-genotypic HCV entry into human hepatocytes by interfering with virion-cell membrane fusion. It was a promising lead compound for the development of novel HCV entry inhibition agents. OBJECTIVE: The aim of the present study is to search for compounds with more potent anti-HCV and antitumor activities and explore SARs. A series of novel derivatives of SA were designed and synthesized and evaluated for in vitro, their anti-HCV and antitumor activities. METHODS: SA derivatives were synthesized by reduction, condensation, esterification or amidation. The anti-HCV activity of title compounds was tested by inhibition on HCVcc infection of Huh7 cells, and a preliminary MOA study was conducted by determining inhibition on HCVpp entry into Huh7 cells. The antitumor activity in vitro was determined by MTT methods. RESULTS: In total, 24 novel derivatives were synthesized. Most of the compounds inhibited HCVcc infection. Compounds 5h and 6 showed the most potent anti-HCVcc activities and inhibition of HCVpp entry into Huh7 cells without obvious cytotoxicity. Most of the title compounds showed potent in vitro antitumor activities against Bel7404 and SMMC7721 tumor cell lines. Compounds 5j and 6 exhibited more potent antitumor activity than positive control SA and DOX. CONCLUSION: Structural modification of SA could lead to the discovery of potent anti-HCV or antitumor agents. Compounds 5h, 5j and 6 were promising lead compounds for development of novel HCV entry inhibition or antitumor agents.

Potential anti-neuroinflammatory NF-кB inhibitors based on 3,4-dihydronaphthalen-1(2H)-one derivatives.

Nuclear factor kappa B (NF-кB) inhibition represents a new therapeutic strategy for the treatment of neuroinflammatory diseases. In this study, a series of 3,4-dihydronaphthalen-1(2H)-one (DHN; 6a-n, 7a-c) derivatives were synthesised and characterised by NMR and HRMS. We assessed the toxicity and anti-neuroinflammatory properties of these compounds and found that 6m showed the greatest anti-neuroinflammatory properties, with relatively low toxicity. Specifically, 6m significantly reduced reactive oxygen species production, down-regulated the expression of NOD-like receptor pyrin domain-containing protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), and caspase-1 and prevented lipopolysaccharide-stimulated BV2 microglia cells polarisation towards an M1 phenotype. Furthermore, 6m significantly decreased IκBα and NF-кB p65 phosphorylation, thus inhibiting the NF-кB signalling pathway. This suggests that 6m may be explored as a functional anti-neuroinflammatory agent for the treatment of inflammatory diseases in the central nervous system, such as multiple sclerosis, traumatic brain injury, stroke and spinal cord injury.

Discovery of novel NF-кB inhibitor based on scaffold hopping: 1,4,5,6,7,8-hexahydropyrido[4,3-d]pyrimidine.

NF-κB is a key signaling pathway molecule linking hepatoma and chronic inflammation. Inhibition of NF-κB activation can alleviate inflammation, and promote hepatoma cell apoptosis. In this study, a series of fluoro-substituted 1,4,5,6,7,8-hexahydropyrido[4,3-d]pyrimidines (PPMs, 31-57) were synthesized from 3,5-bis(arylidene)-4-piperidones (BAPs, 4-30) based on scaffold hopping. We successfully discovered the most potent 43 substituted by electron-withdrawing substitutes (3-F and 4-CF3) exhibited less toxicity and higher anti-inflammatory activity. Preliminary mechanistic studies revealed that 43 induced dose-dependent cell apoptosis at cell and protein level, while inhibited NF-κB activation by suppressing LPS-induced phosphorylation levels of p65, IκBα and Akt, and by indirectly suppressing MAPK signaling, and by inhibiting the nuclear translocation of NF-κB induced by TNF-α or LPS. Docking analysis verified simulated 43 could reasonably bind to the active site of Bcl-2, p65 and p38 proteins. This compound, as a novel NF-κB inhibitor, also demonstrated both anti-inflammatory and anti-hepatoma activities, warranting its further development as a potential multifunctional agent for the clinical treatment of liver cancers and inflammatory diseases.

Duodenal-Jejunal Bypass Ameliorates Type 2 Diabetes Mellitus by Activating Insulin Signaling and Improving Glucose Utilization in the Brain.

BACKGROUND: Duodenal-jejunal bypass (DJB) can dramatically improve type 2 diabetes independent of weight loss and food restriction. Increasing evidence has demonstrated that brain insulin signaling plays an important role in the pathophysiology of type 2 diabetes. This study explores whether the antidiabetic effect of DJB is involved in brain insulin signaling activation and brain glucose utilization. METHODS: A diabetic rat model was established by high-fat and high-glucose diet. DJB or sham surgery was performed in diabetic rats. 18F-FDG PET scanning was used to detect glucose uptake in different organs, particularly in the brain. The levels of glucose transporters, glucose utilization-related proteins (HK1 and PFK2), insulin, and insulin signaling pathway-related proteins (InsR, IRS1/2, PI3K, and p-Akt) in the brain tissues were evaluated and analyzed. RESULTS: The results showed that DJB significantly improved basal glycemic parameters and reversed the decreasing glucose uptake in the brains of type 2 diabetic rats. DJB significantly increased not only the expression levels of brain insulin, IRS1/2, PI3K, and p-Akt but also the levels of the glucose utilization enzymes HK1 and PFK2 in the brain. CONCLUSION: These results indicate that enhanced brain insulin signaling transduction and brain glucose utilization play important roles in the antidiabetic effect of DJB.

Visualisation of the vomerovaginal canal during endonasal transpterygoid approaches and CT imaging diagnosis.

The vomerovaginal canal (VVC) and palatovaginal canal (PVC) are two canals that open forward to the posterior wall of the pterygopalatine fossa (PPF). Although the anatomy and computed tomography (CT) appearances of the PVC have been well studied, the VVC has been rarely reported, especially in endoscopic examinations. Some studies have even failed to distinguish the PVC from the VVC on CT images. The purpose of this study was to demonstrate the anatomy of the VVC on endoscopy and reveal its differences from the PVC, and to analyse the relative positions of the VVC, PVC, and pterygoid canal on CT images. Ten dry skull bases were studied to observe the structures involved in the formation of the VVC. Dissection of four cadaveric heads was performed to demonstrate the anatomy of the VVC on endoscopy. Coronal CT image analysis in 70 patients was conducted to evaluate the distances and relative positions between the VVC, PVC, and pterygoid canal. The PVC and VVC were also compared on axial CT images. The osteological study showed the top wall of the VVC was the antero-inferior wall of the sphenoid sinus. The VVC may be a helpful landmark in endoscopic endonasal transpterygoid approaches. Steps and discrimination in the dissections of the VVC and PVC were described. The interval between the PVC and VVC could be observed on both coronal and axial CT images. The coronal CT images of patients showed differences in the positions and distances among the three canals at both the anterior and posterior apertures of the PVC. The VVC can be easily mistaken for the PVC if its existence is not suspected. The anatomical morphologies and trajectories of the VVC and PVC differed on both nasal endoscopy and CT. The existence of the VVC should be considered during surgery and CT diagnosis within this area.

Oxidative C(sp3)-H functionalization of methyl-azaheteroarenes: a facile route to 1,2,4-triazolo[4,3-a]pyridines.

We herein describe an oxidative [4 + 1] annulation used to prepare 1,2,4-triazolo[4,3-a]pyridines in the presence of I2-DMSO. This protocol enables synthesis of triazolo[4,3-a]pyridine-quinoline linked diheterocycles via a direct oxidative functionalization of sp3 C-H bonds of 2-methyl-azaheteroarenes. The reaction shows a wide substrate scope and good functional group tolerance.

The Effects of Different Catalysts, Substituted Aromatic Aldehydes on One-Pot Three-Component Biginelli Reaction.

AIM AND OBJECTIVE: The Biginelli reaction, first reported in 1893, is one great example of the important multicomponent reactions reported from 1893. Under the same conditions, the influence of the common catalysts on the yield of the Biginelli reaction was investigated. MATERIALS AND METHOD: To a round-bottom flask equipped with a spherical condenser were added 1,3- dicarbonyl compound (1.0 eq), urea (1.45 eq), aromatic aldehyde (1.0 eq), catalyst and methanol. The mixture was heated at reflux for 16 h. After cooling off, the mixture was filtered and washed with cold methanol to give DHPMs. Reaction solution was further purified by recrystallization with petroleum ether and ethyl acetate. Six catalytic systems, different 1,3-dicarbonyl compounds and different substituted aromatic aldehydes with varied substitutions are described for the Biginelli reaction. An analysis was also performed to study the factors that affect the yield of the reaction. RESULTS: When 1,3-dicarbonyl compound was ethyl acetoacetate, the CuCl/ conc.H2SO4 system gave the highest yield (90.5%). While when acetoacetamide was used, the yields of DHPMs in presence of PTSA/conc. HCl, conc. HCl or FeCl3•6H2O were all over 90%. Nine DHPMs with different substituents were obtained. CONCLUSION: The Lewis acid or mixed catalyst had no significant advantage over a single protonic acid as catalyst. Conc. HCl as the catalyst was found to be the most effective condition for the preparation of DHPMs. The aromatic aldehyde with weak electron-withdrawing substituent such as Br resulted in the best yield.

Design, Synthesis and Antibacterial Evaluation of 3-Substituted Ocotillol-Type Derivatives.

Antibiotic resistance has become a serious global problem that threatens public health. In our previous work, we found that ocotillol-type triterpenoid saponin showed good antibacterial activity. Based on preliminary structure-activity relationship, novel serious C-3 substituted ocotillol-type derivatives 7⁻26 were designed and synthesized. The in vitro antibacterial activity was tested on five bacterial strains (B. subtilis 168, S. aureus RN4220, E. coli DH5α, A. baum ATCC19606 and MRSA USA300) and compared with the tests on contrast. Among these derivatives, C-3 position free hydroxyl substituted compounds 7⁻14, showed good antibacterial activity against Gram-positive bacteria. Furthermore, compound 22 exhibited excellent antibacterial activity with minimum inhibitory concentrations (MIC) values of 2 µg/mL against MRSA USA300 and 4 µg/mL against B. subtilis. The structure-activity relationships of all current ocotillol-type derivatives our team synthesised were summarized. In addition, the prediction of absorption, distribution, metabolism, and excretion (ADME) properties and the study of pharmacophores were also conducted. These results can provide a guide to further design and synthesis works.

Novel dissymmetric 3,5-bis(arylidene)-4-piperidones as potential antitumor agents with biological evaluation in vitro and in vivo.

Thirty-five novel dissymmetric 3,5-bis(arylidene)-4-piperidone derivatives (BAPs, 6a-h, 7a-h, 8a-g, 9a-g, 10a-e) were synthesized and evaluated the cytotoxicity. BAPs 6d, 7h, 8g, 9g demonstrated the most potentially inhibitory activities against HepG2 and THP-1 but lower cytotoxicity toward LO2. In vitro, 6d, 7h, 8g, 9g can effectively up-regulate BAX expression, down-regulate Bcl-2 expression in HepG2 cell. They could reasonably bind to the active site of Bcl-2 protein proved by molecular docking modes. The most active BAP 6d induced HepG2 cells apoptosis in a dose-dependent manner by flow cytometrey. The cellular uptake of HepG2 cells showed 6d mainly accumulated into the nuclei by confocal laser scanning microscopy (CLSM). In vivo, 6d suppressed the growth of HepG2 xenografts in nude mice and relatively nontoxic to mice. These results suggest that 6d could be therapeutically beneficial as potential therapeutic agent for the early clinical treatment of liver cancers.

Synthesis and Antibacterial Evaluation of a Series of 11,12-Cyclic Carbonate Azithromycin-3-O-descladinosyl-3-O-carbamoyl Glycosyl Derivatives.

A novel series of 11,12-cyclic carbonate azithromycin-3-O-descladinosyl-3-O-carbamoyl glycosyl derivatives were designed, synthesized, and evaluated for their antibacterial activities in vitro. Most of these compounds had significant antibacterial activity against seven kinds of susceptible strains. In particular, compound G1 exhibited the most potent activity against methicillin-resistant Streptococcus pneumoniae 943 (MIC: 1 µg/mL), Staphylococcus pneumoniae 746 (MIC: 2 µg/mL), Streptococcus pyogenes 447 (MIC: 8 µg/mL), and Escherichia coli 236 (MIC: 32 µg/mL), which were two-, four-, four-, four-, and eight-fold stronger activity than azithromycin, respectively. Additionally, compound G2 exhibited improved activity against methicillin-resistant Staphylococcus aureus MRSA-1 (MIC: 8 µg/mL), Streptococcus pneumoniae 943 (MIC: 2 µg/mL), Staphylococcus pneumoniae 746 (MIC: 2 µg/mL), and Escherichia coli 236 (MIC: 32 µg/mL), which were two-, two-, four-, and eight-fold better activity than azithromycin, respectively. As for methicillin-resistant Staphylococcus aureus MRSA-1, compound G6 presented the most excellent activity (MIC: 4 µg/mL), showing four-fold higher activity than azithromycin (MIC: 16 µg/mL) and erythromycin (MIC: 16 µg/mL). However, compared with other compounds, compounds G7 and G8 with the disaccharide side chain were observed the lower activity against seven strains.

Interaction of heat shock protein 60 (HSP60) with microRNA in Chinese mitten crab during Spiroplasma eriocheiris infection.

Heat shock protein 60 from the Chinese mitten crab Eriocheir sinensis (EsHSP60) was previously identified in relation to Spiroplasma eriocheiris infection by isobaric tags for relative and absolute quantitation labelling followed by liquid chromatography-tandem mass spectrometry. In the present study, to validate the immune function of this protein, the cDNA of the EsHSP60 gene was cloned. Various crab tissues were assessed using real-time PCR, which showed that EsHSP60 transcription occurred in all tissues examined. The expression profiles of EsHSP60 in haemolymph at transcription and protein levels when infected with S. eriocheiris were investigated by real-time PCR and Western blot analysis, respectively. A significant increase of EsHSP60 transcription and protein expression appeared post-injection in response to S. eriocheiris infection when compared to the control group. The double-luciferase reporter gene assay showed that the microRNA PC-533-3p interacted with the 3'-untranslated region of EsHSP60 and inhibited the translation of EsHSP60. The expression profiles of PC-533-3p during S. eriocheiris infection were also investigated by real-time PCR. However, the change tendency of PC-533-3p was opposite to that of the EsHSP60 after S. eriocheiris challenge. These data indicate that the EsHSP60 proteins may play an important role in mediating the immune responses of E. sinensis to an S. eriocheiris challenge.

Synthesis and crystal structures of a 3-acetylated (20S,24S)-ocotillol-type saponin and its C-24 epimer.

In order to study the in vivo protective effect on myocardial ischemia, (20S,24R)-epoxydammarane-12ß,25-diol, (V), and (20S,24S)-epoxydammarane-12ß,25-diol, (VI), were synthesized through a novel synthetic route. Two key intermediates, namely (20S,24R)-3-acetyl-20,24-epoxydammarane-3ß,12ß,25-triol, (III) [obtained as the hemihydrate, C32H54O5·0.5H2O, (IIIa), and the ethanol hemisolvate, C32H54O5·0.5C2H5OH, (IIIb), with identical conformations but different crystal packings], and (20S,24S)-3-acetyl-20,24-epoxydammarane-3ß,12ß,25-triol, C32H54O5, (IV), were obtained during the synthesis. The structures were confirmed by 1H NMR, 13C NMR and HRMS analyses, and single-crystal X-ray diffraction. Molecules of (IIIa) are extended into a two-dimensional network constructed with water molecules linked alternately through intermolecular O-H...O hydrogen bonds, which are further stacked into a three-dimensional network. Compound (IIIb) contains two completely asymmetric molecules, which are linked in a disordered manner through intermolecular C-H...O hydrogen bonds. While the crystal stacks in compound (IV) are linked via weak C-H...O hydrogen bonds, the hydrogen-bonded chains extend helically along the crystallographic b axis.