Good Inhibitory Effect Research Articles

Development and Functional Analysis of Lithocarpus polystachyus (wall.) Rehd Black Tea

This study examined the development conditions and functional properties of a novel compound tea Lithocarpus polystachyus (wall.) Rehd (L. polystachyus, LPR) black tea (LPRBT). The compound tea was developed by fermentation using fresh leaves (Camellia sinensis cv. Qianmei 601) as the main raw material with LPR powder as an additive. Based on the single factor and orthogonal tests with sensory scores as indicators, a withered leaves–LPR powder mass ratio of 9:1 with a 6 h fermentation time was determined to be the production condition of LPRBT with a sensory score of 89.09. In addition, phlorizin content, anti-oxidation function, hypoglycemic function, and tumor suppressor effect of LPRBT were measured. The results demonstrated that LPRBT phlorizin content was significantly higher than apple. It also showed that the equivalent 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radical clearance rate with Vitamin C (Vc) and the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical clearance rate was 81% of Vc. Both hydroxyl and superoxide anion radical clearance increased with the increase in LPRBT amount. LPRBT also showed a good inhibitory effect on α-glucosidase and α-amylase, indicating certain hypoglycemic activity. Moreover, it inhibited the growth of HeLa and A549 cancer cells showing tumor suppressor activity. This study provides a reference for the development and application of LPR food products.

Exploration of Isoquinoline Alkaloids as Potential Inhibitors against Human Islet Amyloid Polypeptide.

Type-2 diabetes mellitus (T2DM) is one of the most concerning public health problems because of its high incidence, multiple complications, and difficult treatment. Human islet amyloid polypeptide (hIAPP) is closely linked to T2DM because its abnormal self-assembly causes membrane damage and cell dysfunction. The development of potential inhibitors to prevent hIAPP fibrillation is a promising strategy for the intervention and treatment of diabetes. Natural isoquinoline alkaloids are used as effective medication that targets different biomolecules. Although studies explored the efficacy of berberine, jatrorrhizine, and chelerythrine in diabetes, the underlying mechanism remains unclear. Herein, three isoquinoline alkaloids are selected to reveal their roles in hIAPP aggregation, disaggregation, and cell protection. All three compounds displayed good inhibitory effects on peptide fibrillation, scattered the preformed fibrils into small oligomers and most monomers, and upregulated cell viability by reducing hIAPP oligomerization. Moreover, combined biophysical analyses indicated that the compounds affected the β-sheet structure and hydrophobicity of polypeptides significantly, and the benzo[c]phenanthridine structure of chelerythrine was beneficial to the inhibition of hIAPP aggregation and their hydrophobic interaction, compared with that of berberine and jatrorrhizine. Our work elaborated the effects of these alkaloids on hIAPP fibrillation and reveals a possible mechanism for these compounds against T2DM.

Synthesis and anti-tumor activity of Fissitungfine B compounds.

In order to explore the potential anti-tumor activity functional molecules, a series of Fissitungfine B derivatives were designed and synthesized. Their anti-tumor activity effects on Hela, MCF-7 and A-549 cell lines were evaluated in vitro. The results showed that some of these Fissitungfine B derivatives exhibited moderate to good anti-tumor activities. Especially, compound 4g with the highest inhibitory activities against all tested cell lines with the Hela was IC50 =3.82 ± 0.56 μM, MCF-7 was IC50 =5.53 ± 0.68 μM, and A-549 was IC50 =4.55 ± 0.53 μM. Furthermore, the compounds 4g have higher inhibitory effects on TDP2 in vitro. In vivo, the biological activities assay results showed that the target compound 4g had a good inhibitory effect on tumor growth. The target compound 4g could inhibit tumor growth well, which might be use as a candidate drug or lead compound for further research and development anti-tumor agents.

An O-Benzyl Phosphonamidate Prodrug of Tenofovir for the Treatment of Hepatitis B Virus Infection

A series of new O-(substituted benzyl) phosphoramidate prodrugs of tenofovir for the treatment of hepatitis B virus (HBV) infections have been designed and synthesized. An investigation of structure-activity relationships revealed that the compound bearing an o-methylbenzyl group (1a) has the most potent in vitro anti-HBV activity. This prodrug (1a) was well-tolerated in KM mice via intragastric administration at a dosage of up to 1.5 g/kg. In DHBV-infected ducks, prodrug 1a displayed a good inhibitory effect on the viral DNA replication in both the serum and the liver in a time- and dose-dependent manner and did not cause any necrosis, hemorrhage, or inflammatory response in the animal livers. Further investigation demonstrated that prodrug 1a achieved a higher exposure of the bioactive metabolite (tenofovir diphosphate, TFV-DP) in the liver, the target organ for the treatment of HBV infection, than tenofovir alafenamide fumarate (TAF) did at an equimolar dose.

New s-Triazine/Tetrazole conjugates as potent antifungal and antibacterial agents: Design, molecular docking and mechanistic study

A novel hybrid N2-(tetrazol-5-yl)-6-substituted-5,6-dihydro-1,3,5-triazine-2,4-diamines have been synthesized in excellent yields through one-pot multi-component reaction of 5-amino-1,2,3,4-tetrazole, cyanamide and aromatic/heteroaromatic aldehydes in acetic acid promoted by controlled microwave heating. All the obtained heterocycles were screened for their antimicrobial and antifungal activities. New series (4a-j) were developed through binding of s-triazine and tetrazole in one compact structure. The tested compounds showed excellent antibacterial activity against the Gram-negative bacterial strains, P. aeruginosa and E. coli compared to ciprofloxacin. The same derivatives experienced high outstanding activity against C. albicans compared to Fluconazole. Investigation of the mode of action as antibacterial agents revealed that the most active compound 4a has good inhibitory effect for DNA gyrase and topoisomerase IV ATPase and E. coli TOPO IV and DNA gyrase supercoiling. Additionally, 4a and 4g showed good in vitro inhibitory activity to lanosterol 14-α-demethylase (CYP51 protein) and good fitting to the same protein as possible antifungal target. Similarly, the target compounds have acceptable ADME and drug-likeness properties without any violation. Hence, new highly potent antibacterial and antifungal candidates were introduced that require further optimization.

The selective depression effect of dextrin on pyrite during the Zn–Fe sulfides flotation under low alkaline conditions

As an environmentally friendly scale inhibitor, characterized by low cost, high efficiency and no secondary pollution, dextrin was utilized as a depressant in the flotation separation of mixed Zn-S concentrate. The microflotation results clearly demonstrate that dextrin exerted a good inhibitory effect on pyrite and sphalerite could be separated successfully from pyrite in low alkaline environment. The mixed mineral flotation results further indicate that sphalerite could be efficiently separated from its synthetic mixture with pyrite via the use of dextrin as the depressant in the pH range of 7–9. The contact Angle test shows that dextrin can be adsorbed on the surface of Cu-activated pyrite to enhance hydrophobicity, but not on the surface of Cu-activated sphalerite. The results of infrared spectroscopy investigations and XPS analyses indicate that under low alkali conditions, copper ions activate sphalerite, and copper sulfide polysulfide forms on sphalerite surface without Cu(OH)2 formation. Cu(OH)2, Fe(OH)2 and CuS were generated on pyrite surface due to the activation of copper ions. The adsorption between dextrin and metal hydroxyl compounds was the main cause of pyrite inhibition， which is attributed to the hydrophilic hydroxyl group in the dextrin molecule. According to these results, dextrin can be used as a selective depressant for pyrite during sphalerite flotation in low alkaline environment.

Bioactive Components from Ampelopsis japonica with Antioxidant, Anti-α-Glucosidase, and Antiacetylcholinesterase Activities

The dried root of Ampelopsis japonica (Thunb.) Makino (A. japonica.) is a traditional medicine used to treat fever, pain, and wound healing. It exhibits anti-inflammatory, antitumor, antityrosinase, and antimelanogenic activities. In this paper, we used different solvent extracts from the root of A. japonica to determine their antioxidant activity. Acetone extract showed relatively strong antioxidant properties by 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazyl (DPPH), superoxide radical scavenging activity, and ferric reducing antioxidant power (FRAP) assays. In addition, these extracts also showed significant α-glucosidase and acetylcholinesterase (AChE) inhibitory activities. Acetone extract significantly inhibited α-glucosidase with an IC50 value of 8.30 ± 0.78 μg/mL, and ethanol extract remarkably inhibited AChE with an IC50 value of 37.08 ± 7.67 μg/mL. Using HPLC analysis and comparison with the chemical composition of various solvent extracts, we isolated seven active compounds and assessed their antioxidant, anti-α-glucosidase, and anti-AChE activities. Catechin (1), gallic acid (2), kaempferol (3), quercetin (4), resveratrol (6), and epicatechin (7) were the main antioxidant components in the root of A. japonica. According to the results of DPPH, ABTS, and superoxide radical scavenging assays, these isolates showed stronger antioxidant capacity than butylated hydroxytoluene (BHT). Moreover, 1, 3, 4, euscaphic acid (5), 6, and 7 also expressed stronger anti-α-glucosidase activity than the positive control acarbose, and all the isolated compounds had a good inhibitory effect on AChE. Molecular docking models and hydrophilic interactive modes for AChE assays suggest that 1 and 5 exhibit unique anti-AChE potency. This study indicates that A. japonica and its active extracts and components may be a promising source of natural antioxidants, α-glucosidase, and AChE inhibitors.

Design, synthesis, and biological evaluation of a new series of pyrazole derivatives: Discovery of potent and selective JNK3 kinase inhibitors

The design, synthesis, and biological activities of a new series of pyrazole derivatives are reported. The target compounds 1a-1w were initially investigated against NCI-60 cancer cell lines. Compounds 1f, 1h, 1k, and 1v exerted the highest anti-proliferative activity over the studied panel of cancer cell lines. Compound 1f showed the most potent activity, and it is more potent than sorafenib in 29 cancer cell lines of different types and more potent than SP600125 against almost all the tested cancer cell lines. It also exerted sub-micromolar IC50 values (0.54–0.98 µM) against nine cell lines. Moreover, the 23 target compounds were tested against Hep3B and HepG2 hepatocellular carcinoma cell lines, of which compounds 1b, 1c, and 1h showed the strongest anti-proliferative activity. The most potent anticancer compounds (1b, 1c, 1f, and 1h) demonstrated a high selectivity towards cancer cells vis-à-vis normal cells. Compounds1f and 1h induced apoptosis and mild necrosis upon testing against RPMI-8226 leukemia cells. Kinase profiling of this series led to the discovery of two potent and selective JNK3 inhibitors, compounds 1c and 1f with an IC50 values of 99.0 and 97.4 nM, respectively. Both compounds showed a good inhibitory effect against JNK3 kinase in the whole-cell NanoBRET assay. This finding was further supported through molecular modeling studies with the JNK3 binding site. Moreover, compounds 1c and 1f demonstrated a very weak activity against CYP 2D6, CYP 3A4, and hERG ion channels.

Design, synthesis and bioactivity evaluation of favorable evodiamine derivative scaffold for developing cancer therapy

Natural product evodiamine is one of the most privileged scaffolds in drug discovery and is suitable for derivatization, which can be conducted quickly for structure optimization and structure-activity relationship research. In this work, a comprehensive SAR study on evodiamine scaffold with N14-3′-fluorophenyl substituted was completed, and compounds with high anti-tumor activity and good inhibitory effect on Top1 and Top2 were screened out. Tested evodiamine derivatives exhibited excellent broad-spectrum anti-tumor activity. Among them, compound 8b revealed 55.15% and 55.50% inhibition for Top1 and Top2 at 25 μM, as well as 0.16 and 0.13 μM IC50 value for MGC-803 and SGC-7901 cells, respectively; compound 9a revealed 70.50% and 71.81% inhibition for Top1 and Top2 at 25 μM, as well as 0.22 and 0.27 μM IC50 value for MGC-803 and SGC-7901 cells, respectively. The further biological evaluation showed that they could functionally induce apoptosis, significantly arrest the cell cycle at the G2/M phase, and markedly inhibit cell proliferation, migration and invasion. In addition, compound 9a performed a tumor inhibitory rate of 36.35% and showed no apparent toxicity in vivo. Overall, these optimized protocols will advance the progression of cancer chemotherapy and can be used to expand the options for screening therapeutic cancer drugs.

Design, synthesis, and biological evaluation of novel carbazole derivatives as potent DNMT1 inhibitors with reasonable PK properties

The DNA methyltransferases (DNMTs) were found in mammals to maintain DNA methylation. Among them, DNMT1 was the first identified, and it is an attractive target for tumour chemotherapy. DC_05 and DC_517 have been reported in our previous work, which is non-nucleoside DNMT1 inhibitor with low micromolar IC50 values and significant selectivity towards other S-adenosyl-L-methionine (SAM)-dependent protein methyltransferases. In this study, through a process of similarity-based analog searching, a series of DNMT1 inhibitors were designed, synthesized, and evaluated as anticancer agents. SAR studies were conducted based on enzymatic assays. And most of the compounds showed strong inhibitory activity on human DNMT1, especially WK-23 displayed a good inhibitory effect on human DNMT1 with an IC50 value of 5.0 µM. Importantly, the pharmacokinetic (PK) profile of WK-23 was obtained with quite satisfying oral bioavailability and elimination half-life. Taken together, WK-23 is worth developing as DNMT1-selective therapy for the treatment of malignant tumour.

Synthesis, Structural Characterization, and Cytotoxic Activity of New Benzo[d]imidazo[2,1-b]thiazole Derivatives Against MCF-7 Breast Cancer Cells.

Breast cancer is an invasive disease with a high prevalence among females. Despite various treatments, studies are still ongoing to find an effective treatment for this disease. This study aimed to synthesize a new series of diaryl benzo[d]imidazo[2,1-b]thiazole compounds containing aminoethoxy side chain and in vitro investigate their cytotoxicity on a human breast cancer cell line (MCF-7). Twelve derivatives (6a-6l) were synthesized from this scaffold, the structures of which were spectroscopically confirmed. The cytotoxic effects of the derivatives on the MCF-7 cell line were also assessed using the MTT assay. All these compounds showed a good inhibitory effect on the MCF-7 cell line, compared to that of tamoxifen. Compounds (6i) and (6j) showed higher cytotoxicity with relevant inhibitory effects of 81% and 73%, respectively.

Screening<italic> Streptomyces </italic>against <italic>Xanthomonas axonopodis</italic> pv<italic>. glycines</italic> and study of growth-promoting and biocontrol effect

<p id="C3">Soybean bacterial pustule disease occurs globally, seriously affecting soybean production. To avoid the many shortcomings of chemical fungicides, the addition of biocontrol bacteria has gradually become an alternative strategy for the prevention and treatment of soybean bacterial pustule disease. However, there are few reports on the development and prevention of soybean bacterial pustule disease biocontrol agents. In this experiment, a total of 186 strains of actinomycetes were isolated from a variety of plant rhizosphere soil samples using the gradient dilution coating method. Eight strains of actinomycete with antagonistic resistance to <italic>Xanthomonas axonopodis</italic> pv. <italic>glycines </italic>(<italic>Xag</italic>) were screened by coculture and Oxford cup methods. Among them, the strain Sl-3 performed the strongest antibacterial activity and the inhibition zone diameter was (32.5±1.5) mm. According to morphological characteristics, physiological and biochemical experiments, 16S rDNA sequencing and phylogenetic analysis, the strain Sl-3 was identified as <italic>Streptromyces lilacinus</italic>. The crude ethyl acetate extract of <italic>Streptromyces lilacinus</italic> Sl-3 has a good inhibitory effect on the growth of <italic>Xag</italic>. The lowest inhibitory concentration of the crude extract was determined to be 64 μg mL ^-1 by 96-well plate method. Scanning electron microscopy revealed that the crude extract of strain Sl-3 had a certain damage effect on <italic>Xag </italic>cells, which affected cell division and cell membrane synthesis, thus inhibiting the growth of bacteria. The crude extract also inhibited the production of<italic> Xag</italic> exopolysaccharide, affected the formation of biofilm, and reduced the toxicity of <italic>Xag</italic> infection. The results of fourier transform infrared spectroscopy showed that the chemical and physiological indexes of lipids, proteins and nucleic acids on the surface of <italic>Xag</italic> cells were affected by crude extract treatment, leading to changes in the structure and composition of <italic>Xag</italic> cell surface substances. The growth promotion test indicated that the fermentation filtrate of the strain Sl-3 can significantly promote the growth of soybean plants. The pot incubation test revealed that the fermentation filtrate of <italic>Streptomyces lilacinus</italic> Sl-3 had a good control effect on soybean bacterial pustule disease with a relative control effect of 93.17%, and the early prevention effect was better than the treatment after the onset.

Identification, biological characterization, and fungicide screening of pathogen causing southern blight in Aster tataricus

This study aims to clarify the species and biological characteristics of the pathogen causing southern blight in Aster tataricus and screen out effective fungicides for the prevention and control of this disease. We collected the typical diseased plants and sclerotia on soil surface for the isolation of the pathogen, and identified the pathogen based on morphological characteristics, molecular biological characteristics, and pathogenicity. Further, we evaluated the inhibitory effects of 12 fungicides on the pathogen by plate growth inhibition assay. In the diseased plants, watery brown spots first appeared at the stem base and then spread upward, which were covered with white mycelia and surrounded by white to yellow-brown sclerotia. From the diseased plants, 15 strains with consistent traits were isolated. The pathogen was identified as Athelia rolfsii based on morphological characteristics and ITS and TEF sequences. The pathogenicity test was carried out according to Koch's rule, which showed the disease symptoms consistent with those in the field. The pathogen presented the optimum growth at 28-30 ℃, pH 5-8, and full darkness. The preliminary indoor screening demonstrated that four chemical fungicides(taifujin, hymexazol, flusilazole, and lime-sulphur-synthelic-solution), two botanical fungiticides(ethylicin and garlic oil), and a microbial agent(Bacillus subtilis) had good inhibitory effects on A. rolfsii. The results of gradient inhibition experiments showed that B. subtilis, flusilazole, and ethylicin had stronger inhibitory activity. The further in vivo screening indicated that ethylicin can be used as the main fungicide for the prevention and treatment of southern blight in A. tataricus.

Analysis of intraoperative EABR characteristics and postoperative efficacy of cochlear implant in patients with tinnitus

Objective:To investigate the characteristics of intraoperative electrically stimulated auditory brainstem responses（EABR） in patients with neural deafness and tinnitus, and to analyze the inhibitory effect of cochlear implantation on tinnitus and its correlation with auditory evoked potential. Methods:Twenty-eight adult patients with neuronal deafness accompanied by tinnitus who underwent cochlear implant surgery in the Peking Union Medical College Hospital from 2014 to 2015 were selected, and 10 age-matched patients without tinnitus with the same age were selected as the control group. Preoperative audiology, imaging and tinnitus history of the patients were retrospectively analyzed. During the operation, EABR were used to detect the auditory central functions at all levels, and the electrophysiological characteristics of the two groups were analyzed. The tinnitus handicap inventory（THI） was used to evaluate the severity of tinnitus before and after surgery, and the correlation between EABR results and THI score was analyzed. Results:There were no postoperative complications such as facial paralysis, cerebrospinal fluid leakage, meningitis, etc. , and electroacoustic reactions were observed in all 38 patients. The results of intraoperative EABR showed that there were significant differences in Ⅲ wave amplitude, Ⅴ wave amplitude and Ⅴ wave latency between tinnitus group and control group（P<0.05）. The mean C value of （162.78± 24.57）CL and the mean intraoperative EABR threshold of （158.62± 10.31） CL were collected in the two groups 12 months after starting the machine, and there was a significant correlation according to linear correlation analysis（r=0.903, P<0.01）. The total THI scores of 28 tinnitus patients were 65.00±14.93, 55.00±15.93 and 36.00±21.02 at three time points before, 1 day after and 1 year after cochlear implantation, respectively. The scores of 1 year after cochlear implantation were significantly different by ANOVA（P<0.05）, but there was no statistically significant difference 1 day after operation（P>0.05）. There was significant correlation between the intraoperative EABR wave Ⅲ amplitude and the linear correlation analysis of THI changes 1 year after operation（r=0.873, P<0.05）. Conclusion:There is significant difference in intraoperative EABR between patients with neural deafness accompanied with tinnitus and patients without tinnitus. Cochlear electrical stimulation has a good inhibitory effect on tinnitus, and intraoperative EABR can be used as a objective assessment tool for cochlear implant to inhibit tinnitus.

The Inhibition Effect of the Expired Esomeprazole on the Corrosion of Carbon Steel in Desalination Water

A study has been carried out to evaluate the effect of expired Esomeprazole (S3O3N19H17C) (20mg) as Inhibitor on the corrosion behaviour of carbon steel in desalination water (Drinking water) by using weight loss technique at room temperature. The test solution used in this study was Desalination water (Drinking water) samples and expired Esomeprazole was used as Inhibitor. The Langelier Saturation Index (LSI) results and the potential pH diagram (Pourbaix diagram) gave an indication that Desalination water sample was a corrosive media. From the study results, it was found that all the weights of the tested specimens were decreased. Furthermore, the results of the carbon steel specimens that were tested in present of inhibitor showed that the weight loss and corrosion rate decreased as the weight of inhibitor increased. The maximum efficiency was found 52.08% when the weight of inhibitor was 2.0055g which was the maximum weight and the minimum corrosion rate was 0.0046cm/year. So, it was assumed that the expired Esomeprazole has good inhibition effect on the corrosion of carbon steel.

Discovery of precision targeting EZH2 degraders for triple-negative breast cancer

EZH2 is usually overexpressed in TNBC and other tumors, which has a great influence on the occurrence, development and prognosis of tumors. However, current EZH2 inhibitors, including Tazemetostat and GSK126, affect the methyl catalytic capacity of EZH2 and have little effect on the tumorigenic activity of EZH2 itself, resulting in poor efficacy against most solid tumors. Herein, we designed and optimized proteolytic targeting chimeras (PROTACs) precision targeting EZH2. The most active PROTAC molecule U3i has a high affinity for PRC2 complex (KD = 16.19 nM) and show good inhibitory effects on MDA-MB-231 (IC50 = 0.57 μM) and MDA-MB-468 (IC50 = 0.38 μM) cells. Compared with that of the GSK126, the growth inhibitory activities of U3i against these two TNBC cells increased by approximately 20- and 30-fold. Further studies showed that U3i can degrade PRC2 complex in TNBC cells, induce apoptosis, and cause little damage to normal cells. Therefore, U3i is a potential anticancer molecule for TNBC treatment.

Long term antibacterial effect cellulose film was modified with polyhexamethylene biguanide (PHMB)

Cellulose products such as textile, paper, package and so on are apt to breed bacterial. In this study, AA-PHMB antibacterial agent was synthesized innovatively. It was grafted onto cellulose by the addition polymerization of carbon carbon double bonds and hydroxyl groups to prepare cellulose antibacterial film with excellent performance. The structures, elements, mechanical properties and antibacterial activities of films were studied. The results showed that CN absorption at 1631 cm−1 of guanidine and the amide group absorption peak at 1554 cm−1 appeared on cellulose graft copolymers; employing SEM-EDS, a great quantity of deposited materials, with the elements of C, O and N, were observed on the grafted cellulose. The graft percentage of cellulose-AA-PHMB was about 62%. Compared with unmodified cellulose films, the mechanical properties of PHMB-AA-cellulose film were lower, and the crystallinity of the PHMB-AA-cellulose film was lower than that of original cellulose film. The modified film as a raw material had a good inhibitory effect on Escherichia coli and Staphylococcus aureus was proved by bacteriostatic experiments. Under the condition of continuous culture for 15 days, it still had a good bacteriostatic effect on the above strains, and therefore the cellulose-AA-PHMB films were long term antibacterial effect materials.

The preparation and characterization of electrospun gelatin nanofibers containing chitosan/eugenol-sulfobutyl-β-cyclodextrin nanoparticles

In this study, a multifunctional food packaging material (G-Eug-NPs-NF) based on gelatin nanofiber membranes (G-NF) containing eugenol nanoparticles (Eug-NPs) were prepared. The Eug-NPs were fabricated through the electrostatic self-assembly by using two ionic polysaccharides chitosan and sulfobutylether-β-cyclodextrin (SCD). Compared with G-NF, the G-Eug-NPs-NF exhibited better antioxidant capacity, which positively correlated with Eug-IC concentration, up to 84.17%. In addition, the latter had a good inhibitory effect on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), and was more conducive to inhibit the growth of S. aureus. At the same time, the sustained release experiment showed that the incorporation of Eug-NPs in nanofiber membranes improved the sustained release ability of G-Eug-NPs-NF. G-Eug-NPs-NF exhibits the promising application of Eug in food, medicine and other fields.

A novel aromatic amide derivative SY-65 co-targeted tubulin and histone deacetylase 1 with potent anticancer activity in vitro and in vivo

Given the essential role of Epigenetic regulation in many biological processes, targeted epigenetic drugs have been gradually applied to the treatment of tumors. Histone deacetylases (HDACs) are a class of epigenetic enzymes, which play key roles in chromosome structural modification and gene expression regulation. Targeted microtubules drugs have achieved great success in clinical application for decades. Development of novel agents with multitargeting capabilities specially dual-target has become a popular research field for the treatment of human cancers, which may provide synergistic anticancer effects. Here, we reported a novel aromatic amide derivative SY-65 co-targeted tubulin and histone deacetylase 1 with potent anticancer activity in vitro and in vivo. Compound SY-65 was identified as a dual inhibitor of tubulin/HDAC1 (IC50 = 3.64 and 0.529 μM, respectively) with excellent antiproliferative activity against MGC-803, HCT-116, KYSE-450, HGC-27, SGC-7901 and MKN-45 cells. Especially, compound SY-65 exhibited potent antiproliferative activity against MGC-803, HGC-27 and SGC-7901 cells with IC50 values <55 nM, which was better than that of Colchicine, MS-275 and SAHA. Compound SY-65 effectively inhibited tubulin polymerization and bound to the colchicine binding site of tubulin, as well as inhibited HDAC1 activity both intra/extracellularly. Molecular docking results suggested there were the well-defined binding modes of compound SY-65 in HDAC1 and tubulin. In addition, compound SY-65 inhibited colony formation, interfered with the cell cycle distribution, induced cell cycle arrest at the G2/M phase and apoptosis in MGC-803 and HGC-27 cells. Compound SY-65 also exhibited a good tumor inhibitory effect in vivo without obvious toxicity. Therefore, compound SY-65 could be developed as a novel tubulin/HDAC1 candidate inhibitor for future cancer therapeutics.

Experimental Study on Two-Phase Explosion Suppression of Gas/Pulverized Coal by Explosion Suppressant.

Pulverized coal is widely distributed in coal mine roadways, which can enhance the power of a gas explosion. Explosion suppression technology can effectively reduce the explosion power. At present, rock powder shed, a water bag, and ABC powder are widely used in most coal mine explosion suppression technologies. In order to verify the explosion suppression effect of rock powder, water, and ABC powder in the pulverized coal environment, a series of experiments on a suppressing gas/pulverized coal two-phase explosion were carried out with a self-built large-scale gas explosion experimental system. The experimental study in this paper can provide some reference for the improvement of explosion suppression technology in coal mines. In this paper, through the suppression of a secondary explosion, flame, and impact of pulverized coal, the explosion suppression effects of three kinds of explosion suppressants are comprehensively analyzed. The results show that rock powder has a good inhibitory effect on a secondary explosion and flame of pulverized coal, and water has a good inhibitory effect on the shock wave. ABC powder has the best explosion suppression effect; the inhibition of a secondary explosion of pulverized coal is 4.17 times that of rock powder, the inhibition of flame is 4.28 times that of rock powder, and the inhibition of shock wave is 2.24 times that of water.