Search

[Display omitted] Monocyclic β-lactams are stable to a number of β-lactamases and are the focus of researchers for the development of antibacterial drugs, particularly against Enterobacterales. We recently synthesized and reported the bactericidal activity of diverse series of aztreonam appended with amidine moieties as siderophores. One of the derivatives exhibiting the highest MIC value in vitro was selected for further preclinical studies. The compound DPI-2016 was reassessed for its synthetic routes and methods that were improved to find the maximum final yields aimed at large-scale synthesis. In addition, the results of the pharmacological studies were determined with reference to aztreonam. It has been found that the compound DPI-2016 showed comparable or slightly improved ADMET as well as pharmacokinetic parameters to aztreonam. It is estimated that the compound could be a potential lead for further clinical evaluation. [ABSTRACT FROM AUTHOR]

Avibactam is a clinically approved non‐β‐lactam based β‐lactamase inhibitor. Derivatization of this scaffold with improved inhibition profile is the demand of the day to cope with the future challenges. We successfully synthesized new derivatives of avibactam containing sulfonylamidine moieties at C2 position of the diazabicyclooctane ring. We tested in vitro antibacterial activities of newly synthesized compounds against 10 bacterial strains expressing variable β‐lactamases. All compounds did not exhibit antimicrobial profile when assayed individually; however, all compounds minimized the MIC value of the imipenem in combination. Compound 5l proved most potent against all 10 bacterial strains, and showed improved inhibition against six bacterial strains as compared with the control inhibitor, relebactam. The compound 5l may be a lead hit for future development. [ABSTRACT FROM AUTHOR]

Background. Owing to the intrinsic stability against common β-lactamases and metallo-lactamases, monobactams gathered special attention in antibiotic drug development. However, so far, aztreonam is the only monobactam approved by FDA for clinical use. We designed new derivatives of aztreonam to enhance its antibacterial efficacy. Methods. We synthesized a series of monocyclic β-lactams by modifying mainly at the C3 position of azetidinone ring. NH2 group at C3 of azetidinone was attached to thiazole and thiadiazole which in turn was linked to nitrogenous heterocyclic rings via amidine moieties. We then investigated the in vitro antibacterial activities of synthesized compounds against ten bacterial strains of clinical interest in comparison to aztreonam and ceftazidime. Results. All compounds showed improved antibacterial activities against tested strains compared to reference drugs. Compounds 14d and 14e were most potent and showed the highest potency against all bacterial strains, with MIC values ranging from 0.25 µg/mL to 8 µg/mL, as compared to aztreonam (MIC 16 µg/mL to >64 µg/mL) and ceftazidime (MIC >64 µg/mL). These compounds (14d and 14e) may be valuable lead targets against multidrug-resistant Gram-negative bacteria. [ABSTRACT FROM AUTHOR]

P leurotus eryngii ( P . eryngii), also known as the king oyster mushroom, contains many bioactive substances, including polysaccharides, lipids, peptides, sterols and triterpenoids. The aim of this study was to explore the antitumor and immunomodulatory activities of P . eryngii extract. The fresh P . eryngii material was extracted with MeOH (methanol) and then partitioned with EtOAc (ethyl acetate). The study showed that the P . eryngii EtOAc extract ( EAe) not only has antitumor effects by in vitro and in vivo methods but also significantly increases some immune activities. In addition, histopathological observations showed that EAe-treated mice exhibited much lower cancerization throughout the liver and lung. EAe can also promote antioxidant activity, which may regulate the body's antioxidant capacity and activate the antitumor mechanism. Practical Applications Our study revealed the anticancer and immunomodulatory activity of P leurotus eryngii extract, and identified the key components of the P . eryngii extract with HPLC-MS. These findings explain the antitumor activity of P . eryngii, which is very useful for developing the potential antitumor drugs for clinical application. [ABSTRACT FROM AUTHOR]

Abstract: A practical three-component copper-mediated oxidative trifluoromethylthiolation of aryl boronic acids with cheap and readily available sodium trifluoroacetate and elemental sulfur is reported. A variety of trifluoromethylthio-substituted aromatics are synthesized in moderate yields under mild reaction conditions. [Copyright &y& Elsevier]

Abstract: This study was designed to evaluate the effect of oral administration of ginseng stem-and-leaf saponin (GSLS) on immune responses in chickens vaccinated with live Newcastle disease (ND) vaccines. In experiment 1, chickens were orally administered GSLS (2.5, 5, 10, and 20mg/kg) in drinking water for 3 days, and then intranasally vaccinated with ND vaccine. Hemagglutination inhibition (HI) test showed that the optimal dose of GSLS for enhancing HI titers was 5mg/kg. In experiment 2, chickens were fed with GSLS (5mg/kg) for 7, 5 or 3 days before vaccination. Result indicated that GSLS enhanced HI titers in a time-dependent manner. The order of the duration for drinking GSLS on increasing HI titers was 7 days>5 days>3 days. In experiment 3, chickens were fed with GSLS before or after immunization. Serum was sampled at a week interval for 5 weeks for HI test, splenic lymphocytes were prepared at weeks 2 and 4 after the booster immunization for lymphocyte proliferation test (LPT) and intestinal tissues were sampled at week 4 after the booster immunization for immunohistochemistry and histological examination. Results showed that HI titer, LPT, IgA+ cells and intestinal intraepithelial lymphocytes (iIELs) were significantly higher in chickens drinking GSLS before vaccination than those after vaccination. Therefore, oral administration of GSLS in drinking water at a dose of 5mg/kg for 7 days significantly increased systemic as well as gut mucosal immunity in chickens immunized with ND vaccine. Considering the immune potentiating effect of GSLS on ND vaccine, GSLS should be evaluated for its oral adjuvant effect on the immune response against other diseases such avian influenza and infectious bursal disease. [Copyright &y& Elsevier]

• The principle of signal purification (SP) is presented, aiming to obtain pure unbalance information under rotating-frequency (1X) vibration interference. • The SP-based vibration suppression method, which can correct the unbalance fault more thoroughly, is proposed and implemented. • The experimental results meet expectations, effective suppression of unbalanced vibration is achieved. The work described in this manuscript are beneficial for improving the accuracy of various balancing methods. Unbalance faults of a rotor owing to various factors such as manufacturing imperfections, installation errors, and material inhomogeneity, cannot be avoided. Unbalance-induced vibration generally constitutes the majority of the total undesired vibrations. Thus, controlling the unbalance-induced vibration is vital to fully utilizing rotating equipment. This paper presents a novel method for solving the dynamic balancing problem of a rotor under the interference of other rotating-frequency (1X) faults. First, the vibrational behaviour of the multi-fault rotor is analysed. Thereafter, the principle for signal purification (SP) is proposed, with the aim of obtaining pure unbalance information under 1X vibration interference. Signal resampling and spectrum correction are employed to purify the signal. Finally, an SP-based suppression method for the unbalanced vibration of a rotor with multiple 1X faults is proposed. The effectiveness of the proposed method was validated by comparing its balancing effects with those of the traditional method on a rotor test platform. The experimental results demonstrated that the proposed method eliminates the unbalance fault of the rotor more thoroughly than the traditional method and maintains the effect of vibration suppression at higher speeds. [ABSTRACT FROM AUTHOR]

Inexpensive sodium trifluoroacetate and elemental sulfur are employed as reagents to access aryl trifluoromethyl thioethers through an oxidative decarboxylative pathway. [ABSTRACT FROM AUTHOR]

Vaccination is an important approach to the control of foot-and-mouth disease (FMD). This study evaluated the effect of oral administration of ginseng stem–leaf saponins (GSLS) on the immune response to FMD vaccine and the gut mucosal immunity in mice. In experiment 1, mice were orally administered GSLS or not treated as a control. The animals were then immunized twice with FMD vaccine. Blood was sampled weekly within five weeks after the boost immunization for measurement of serum IgG and the isotypes. In experiment 2, mice were orally administrated GSLS or not treated as a control. After that, splenocytes were prepared from sacrificed mice for lymphocyte proliferation assay and intestinal tissues were sampled for immunohistochemistry and histological examination. The results showed that oral administration of GSLS significantly enhanced serum IgG and the isotype responses to FMD vaccine as well as the number of intestinal intraepithelial lymphocytes (IELs) and immunoglobulin A (IgA)+ cells. Therefore, GSLS may be a potent oral adjuvant and deserve further study to improve vaccination in susceptible animals. [ABSTRACT FROM PUBLISHER]

The diazabicyclooctane (DBO) has emerged as the attractive motif for the development of new β-lactamase inhibitors after the clinical approval of avibactam and relebactam. We are striving at improving the lactamase inhibition strength and antibacterial spectrum of the DBO derivatives. We synthesized the substituted-amidine derivatives (5a–5j) of the DBO, and determined the antibacterial efficacy of the two β-lactam drugs i.e. imipenem and meropenem, in combination with compounds 5a–5j. All these derivatives lowered the MIC values of the imipenem and meropenem, indicating their β-lactamase inhibition profile, however in variable strength. The best results were obtained when the compounds 5a–5j were combined with meropenem indicating the better association of these compounds with meropenem in comparison to imipenem. With meropenem, compounds 5a and 5b proved to be the most potent exhibiting the highest antibacterial efficacy against five out of ten microbial strains. Moreover, the MIC data showed that β-lactamase inhibition strength of compounds 5a and 5b was comparable to relebactam in eight out of ten bacterial strains. [ABSTRACT FROM AUTHOR]

Our previous study identified a chickpea peptide (CPe-III) derived from chickpea albumin hydrolysate which exhibited a high antioxidant activity. CPe-III-S peptide corresponding to amino acid sequences of CPe-III (RQSHFANAQP) was synthesized chemically to determine the bioactive activity. The reducing power, hydroxyl radical, DPPH radical, ABTS radical scavenging assay and DCFH-DA assay showed significant dose-dependent activities. The cell viability assay indicated a high inhibition activity on MCF-7 and MDA-MB-231 cells with EC 50 values of 2.38 and 1.50 μmol/mL. The p53 protein increased with increasing concentration of CPe-III-S tested by ELISA Kit. The specific binding of peptide and p53 protein was determined by means of molecular docking. These results indicated that CPe-III-S effectively inhibited the proliferation of breast cancer cells by increasing the p53. This is the first report of the synthetic peptide which based on CPe-III derived from the enzymatic hydrolysate of chickpea to exhibit the antioxidant activity and antiproliferative effect. [ABSTRACT FROM AUTHOR]

Antibacterial resistance towards the β-lactam (BL) drugs is now ubiquitous, and there is a major global health concern associated with the emergence of new β-lactamases (BLAs) as the primary cause of resistance. In addition to the development of new antibacterial drugs, β-lactamase inhibition is an alternative modality that can be implemented to tackle this resistance channel. This strategy has successfully revitalized the efficacy of a number of otherwise obsolete BLs since the discovery of the first β-lactamase inhibitor (BLI), clavulanic acid. Over the years, β-lactamase inhibition research has grown, leading to the introduction of new synthetic inhibitors, and a few are currently in clinical trials. Of note, the 1, 6-diazabicyclo [3,2,1]octan-7-one (DBO) scaffold gained the attention of researchers around the world, which finally culminated in the approval of two BLIs, avibactam and relebactam, which can successfully inhibit Ambler class A, C, and D β-lactamases. Boronic acids have shown promise in coping with Ambler class B β-lactamases in recent research, in addition to classes A, C, and D with the clinical use of vaborbactam. This review focuses on the further developments in the synthetic strategies using DBO as well as boronic acid derivatives. In addition, various other potential serine- and metallo- β-lactamases inhibitors that have been developed in last few years are discussed briefly as well. Furthermore, binding interactions of the representative inhibitors have been discussed based on the crystal structure data of inhibitor-enzyme complex, published in the literature. [ABSTRACT FROM AUTHOR]

Avibactam is a non‐β‐lactam based second generation β‐lactamase inhibitor containing diazabicyclooctane (DBO) ring as the β‐lactam mimic. We substituted C2 position of DBO scaffold by a number of amidine derivatives to form water soluble final compounds A1‐A14. The synthesized compounds were evaluated for their antibacterial and synergistic activity in combination with an antibiotic in vitro. The compounds, were tested against ten bacterial strains alone and in combination with existing antibiotic, meropenem. All compounds didn't show antibacterial activity when alone (MIC,>128 μM), however exhibited moderate to good synergistic activity in the presence of meropenem by lowering its MIC values. Compound A7 proved the most potent among other counterparts against all bacterial species with MIC from <0.29 μM to 2.34 μM, and showed comparable or improved activity to avibactam against eight bacterial strains. Compound A7 may prove a lead for next level in vivo and clinical studies. [ABSTRACT FROM AUTHOR]

Polyfunctional pyridines are backbone of numerous natural products and pharmaceutical reactive intermediates. We have developed an iron‐catalyzed cyclization reaction between ketoxime carboxylates and nitrones to afford trisubstituted pyridines. Employing this strategy, we have synthesized a number of trisubstituted pyridines with various functional groups in good yields under simple reaction conditions. It is worth mentioning that the nitrones can serve as a novel C1 unit in organic synthesis. [ABSTRACT FROM AUTHOR]

[Display omitted] New avibactam derivatives in which amide moiety is replaced by substituted amidine groupings were obtained in several steps, the key step having involved the conversion of 2-positioned cyano group of the 1,6-diazabicyclo[3.2.1]-octane framework into the amidine one. Synergistic antibacterial activity of the new compounds in combination with meropenem infers the agonistic effect of these derivatives against β-lactamases. [ABSTRACT FROM AUTHOR]

Traditional cancer therapy is mainly targeting on enhancing cell apoptosis, however, it is well established that many cancer cells are chemo-resistant and defective in apoptosis induction. Therefore, it may have important therapeutic implications to exploit some novel natural compounds based on non-apoptotic programmed cell death. Currently, accumulating evidence shows that the compounds from nature source can induce non-apoptotic programmed cell death in cancer cells, and therefore these natural compounds have gained a great promise for the future anticancer therapeutics. In this review, we will concentrate our efforts on the latest developments regarding major forms of non-apoptotic programmed cell death--autophagic cell death, necroptosis, ferroptosis, pyroptosis, glutamoptosis and exosome-associated cell death. Our increased understanding of the role of natural compounds in regulating non-apoptotic programmed cell death will hopefully provide prospective strategies for cancer therapy. [ABSTRACT FROM AUTHOR]

[Display omitted] 2- O -β- d -glucopyranosyl- l -ascorbic acid (AA-2βG) provides a source of sustained release of ascorbic acid (vitamin C) upon α-glucosidase activity inside the human body, and is therefore an ingredient of cosmetics, food, and medicinal products. Commercial synthesis of the compound is highly demanded and is attempted from time to time, aimed at improved and commercially viable strategies. We synthesized the AA-2βG in five steps starting from ascorbic acid with a 31.4% overall yield. The synthetic steps do not need column purification except one, and the final product is pure enough to be utilized for application purposes. [ABSTRACT FROM AUTHOR]

Background: The electroacupuncture (EA) with different number of points significantly affected its efficacy on knee osteoarthritis (KOA), and the severity of KOA also influenced its response to treatments. Hence, we prospectively compared the clinical efficacy of EA on KOA with different severities. Methods: A total of 132 KOA patients recruited from 181st Central Hospital of The Chinese People's Liberation Army between March 2014 and March 2015 were classified into 4 KOA stages according to Kellgren Lawrence grading scale. They were allocated into three treatment groups, including two-point group, four-point group and sixpoint group. Patients in the six-point group received treatment at six-points including ST34, SP10, SP9, ST36, ST35 and EX-LE4. Patients in the four-point group received treatment at ST34, SP10, ST35 and EX-LE5, while patients in the two-point group received treatment at ST35 and EX-LE4. Visual Analog Scale (VAS), McMaster Universities Osteoarthritis Index (WOMAC) and self-assessment questionnaire of patients were assessed after treatment. Results: Three kinds of EA treatments all have significant clinical effects on KOA patients with down-regulated scores of VAS and WOMAC. Regarding post-treatment efficacy, the six point group exhibited lower VAS score and higher WOMAC score compared with the other two groups. For patients with different KOA grades, patients with higher KOA grades were associated with lower grade of treatment efficacy. Conclusions: Patients with KOA, especially those with lower KOA stages, could gain beneficial efficacies from EA treatments with two, four and six points, respectively. [ABSTRACT FROM AUTHOR]

We previously demonstrated that the antineoplastic agent docetaxel enhanced the immune response to an influenza vaccine. This study evaluated the adjuvant effect of docetaxel (DOC) on the therapeutic efficacy of HPV16 L2E6E7 fusion protein (HPV-LFP) in mice inoculated with TC-1 cells. The results demonstrated that docetaxel significantly enhanced the therapeutic effect of HPV-LFP on TC-1 cell-induced tumors in mice. The injection of HPV-LFP in combination with docetaxel in TC-1 tumor-bearing mice significantly reduced tumor volume and weight, and a greater percent survival was detected than mice treated with HPV-LFP alone. The inhibition of tumors was associated with significantly increased serum antigen-specific IgG and isotypes, activated CTLs, increased IFN-γ-secreting T cells, and decreased Treg cells and IL-10-secreting cells in spleen. In addition, down-regulation of IL-10, VEGF and STAT3, up-regulation of IFN-γ and decreased Treg cells in the tumor microenvironment may also important contributing factors to the antitumor effect. It may be valuable to use a DOC-containing water to dilute HPV-LFP powder before injection in patients because of its excellent adjuvant effect on HPV-LFP and solubility in water. [ABSTRACT FROM AUTHOR]

Vaccination using attenuated vaccines remains an important method to control animal infectious diseases. The present study evaluated ginseng stem-leaf saponins (GSLS) and thimerosal (TS) for their adjuvant effect on an attenuated pseudorabies virus (aPrV) vaccine in mice. Compared to the group immunized with aPrV alone, the co-inoculation of GSLS and/or TS induced a higher antibody response. Particularly, when administered together with GSLS-TS, the aPrV vaccine provoked a higher serum gB-specific antibody, IgG1 and IgG2a levels, lymphocyte proliferative responses, as well as production of cytokines (IFN-γ, IL-12, IL-5 and IL-10) from lymphocytes, and more importantly provided an enhanced cytotoxicity of NK cells and protection against virulent field pseudorabies virus challenge. Additionally, the increased expression of miR-132, miR-146a, miR-147 and miR-155 was found in murine macrophages cultured with GSLS and/or TS. These data suggest that GSLS-TS as adjuvant improve the efficacy of aPrV vaccine in mouse model and have potential for the development of attenuated viral vaccines. [ABSTRACT FROM AUTHOR]

Abstract: Fifty-six mice were randomly divided into four groups with 14 mice in each. Two groups were subcutaneously injected twice with a foot-and-mouth disease vaccine with 2-week intervals; each of them had been orally administered 0.89% saline or Atractylodis macrocephalae Koidz. polysaccharides (RAMPS) 0.05g for 4 days before immunization. The rest were not immunized but treated in the same way. One-week after the primary and two weeks after the booster immunization, half in each group were sacrificed to measure serum IgG and the parameters for the intestinal mucosal immunity. Results indicated that oral administration of RAMPS increased both serum specific IgG response and intestinal mucosal immunity as shown by elevated total sIgA, mRNA expression of TGF-β, IL-6, TNF-α, IgA+ cells and intestinal intraepithelial lymphocytes in duodenum. It is suggested that increased serum IgG response may be associated with enhanced local mucosal immunity by oral administration of RAMPS. [Copyright &y& Elsevier]

[Display omitted] Monobactams play an important role in antibiotic drug discovery. Based on the structural characteristics of aztreonam and its biological targets, six new monobactam derivatives (2a-c and 3a-c) were synthesized and their in vitro antibacterial activities were investigated. Compounds 2a-c showed higher activities against tested gram-negative bacteria than that of parent aztreonam. Monobactam 2c exhibited the most potent activities, with MIC ranging from 0.25 to 2 μg/mL against most bacteria. [ABSTRACT FROM AUTHOR]