High Antiplasmodial Activity of Golden Gamat (S.hermanni) Extract Through In Vitro Study

S.hermanni is a marine biota that contains active components that are anti-fungal, anti-bacterial, antioxidant, anti-inflammatory, and anti-cancer. The research focused on examining the antiplasmodial activity of an ethanol extract of S. hermanni on the proliferation of P. falciparum in vitro. The total sample size was 30 mediums, which included: (G1). No extract or chloroquine administration in the P.falciparum medium (G2). Chloroquine treatment administration on P. falciparum medium (G3). P. falciparum medium with S. hermanni extract. Parasitaemia, growth percentage, inhibitory rate, and IC50 were among the parameters evaluated. Administration of extract serial doses succeeds in reducing the percentage of parasite growth and parasitemia levels. G3 demonstrated an inhibitory rate of 88.51 % with a dose of 100 µg/ml and an IC50 of 2.86 µg/ml, indicating high antimalarial activity, although chloroquine had greater antimalarial activity than S. hermanni extract. In vitro studies on S hermanni, ethanol extract indicated that it contains bioactive components and can be an effective antiplasmodial agent.

Discovery of Cysteine and Its Derivatives as Novel Antiviral and Antifungal Agents

Based on the structure of the natural product cysteine, a series of thiazolidine-4-carboxylic acids were designed and synthesized. All target compounds bearing thiazolidine-4-carboxylic acid were characterized by 1H-NMR, 13C-NMR, and HRMS techniques. The antiviral and antifungal activities of cysteine and its derivatives were evaluated in vitro and in vivo. The results of anti-TMV activity revealed that all compounds exhibited moderate to excellent activities against tobacco mosaic virus (TMV) at the concentration of 500 μg/mL. The compounds cysteine (1), 3–4, 7, 10, 13, 20,23, and 24 displayed higher anti-TMV activities than the commercial plant virucide ribavirin (inhibitory rate: 40, 40, and 38% at 500 μg/mL for inactivation, curative, and protection activity in vivo, respectively), especially compound 3 (inhibitory rate: 51%, 47%, and 49% at 500 μg/mL for inactivation, curative, and protection activity in vivo, respectively) with excellent antiviral activity emerged as a new antiviral candidate. Antiviral mechanism research by TEM exhibited that compound 3 could inhibit virus assembly by aggregated the 20S protein disk. Molecular docking results revealed that compound 3 with higher antiviral activities than that of compound 24 did show stronger interaction with TMV CP. Further fungicidal activity tests against 14 kinds of phytopathogenic fungi revealed that these cysteine derivatives displayed broad-spectrum fungicidal activities. Compound 16 exhibited higher antifungal activities against Cercospora arachidicola Hori and Alternaria solani than commercial fungicides carbendazim and chlorothalonil, which emerged as a new candidate for fungicidal research.

Synthesis and anti-acetylcholinesterase activities of novel glycosyl coumarylthiazole derivatives

Eleven glycosyl coumarylthiazole derivatives are synthesized by cyclization and condensation of glycosyl thiourea with 3-bromoacetyl coumarins in ethanol. The reaction conditions are optimized and good yields of products (80%–95%) are obtained. The structures of all new products were confirmed by IR, 1H and 13C NMR, and by HRMS (electrospray ionization). The in vitro acetylcholinesterase (AChE) inhibitory activities of these new compounds are tested by Ellman’s method. Among them, N-(2-acetamido-3,4,6-tri- O-acetyl-2-deoxy-β-D-glucopyranosyl)-4-(6-nitrocoumarinyl)-1,3-thiazole-2-amine showed the best activity with an in vitro AChE inhibitory rate of 58% and an IC50 value of 12 ± 0.38 μg/mL.

In Vitro Screening and Transfection Concentration Optimization of Cynomolgus Monkey IκBα-siRNA

Purpose. To seek for a small interfering RNA (siRNA) sequence targeting a cynomolgus monkey inhibitor of nuclear factor kappa B α (IκBα) that can specifically and effectively suppress IκBα gene expression of cynomolgus monkey ciliary muscle (CM) cells and trabecular meshwork (TM) cells in vitro and screen for optimal siRNA transfection concentration. Methods. Three IκBα-specific double-stranded siRNAs were designed and synthesized. They were transfected into primarily cultured cynomolgus monkey CM cells and TM cells. The mRNA and protein levels of IκBα were examined by using real-time quantitative polymerase chain reaction (real-time PCR) and western blot to screen a pair of candidate valid sequences with the highest inhibitory rate. Both cells were transfected with Cy5-labeled nonspecific control-siRNA (NC-siRNA) of four different concentrations (10, 20, 50, and 100 nmol/L(nM)), and flow cytometry was used to assess transfection efficiency. Then, cells were transfected with the candidate valid IκBα -siRNA of the same four concentrations, and the cytotoxicity was detected by using Cell Counting Kit-8 (CCK8), and the inhibitory efficiency of IκBα was identified via real-time PCR to find out optimal siRNA transfection concentration. Results. The suppression effect of the siRNA targeting the GCACTTAGCCTCTATCCAT of IκBα gene was most obvious by in vitro screening. The inhibitory rate of IκBα was 82% for CM cells and 82% for TM cells on the mRNA level and 98% for CM cells and 93% for TM cells on the protein level, respectively. The results of flow cytometry showed that the transfection efficiency was the highest at 100 nM, which was 89.0% for CM cells and 48.2% for TM cells, respectively. The results of CCK8 showed that there was no statistically significant difference in cell viability after transfection of different concentrations of IκBα-siRNA. The results of real-time PCR indicated that there was no statistical difference in the inhibitory efficiency of IκBα after transfection of different concentrations of IκBα-siRNA. Conclusion. It proves that the siRNA targeting the GCACTTAGCCTCTATCCAT of IκBα gene is the valid sequence to suppress cynomolgus monkey IκBα expression of CM cells and TM cells by RNAi. 10 nM is the optimal transfection concentration.

Synthesis and antibacterial activity of modified ε-polylysine

In this paper, Ugi reaction was used to synthesize the modified polylysine (M-ε-PL) in two steps, and OD value was measured by ultraviolet spectrophotometer to determine the inhibitory rate of M-ε-PL in different concentrations of Escherichia coli and Staphylococcus aureus. The results showed that the antibacterial effect was better with the increase of concentration of M-ε-PL. Among them, 20 mg/mL M-εPL had better bacteriostatic effect on E. coli and S. aureus. The antibacterial rate was 70% and 44%.

Synthesis and AChE inhibitory activity of N-glycosyl benzofuran derivatives

Six N-glycosyl benzofuran derivatives were synthesized by the catalysis of organic bases and condensation agents. The benzofuran derivatives were obtained by the reaction of various salicylaldehydes in acetone, and then hydrolyzed to the corresponding carboxylic acids. Finally, the target compounds were synthesized by acylation and the reaction conditions were optimized. The acetylcholinesterase (AChE) inhibitory activity of the desired compounds was tested using Ellman’s method. Most of the compounds showed acetylcholinesterase-inhibition activity; N-(2,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl)benzofuran-2-carbxamide (5a) showed the best acetylcholinesterase inhibition, with an inhibitory rate of 84%.

Flow Cytometry for Evaluation of EGFR-mTOR Signal Way in the Growth Inhibitory Rate of Hela Cell Under Low Glucose and High Lactic Acid Environment

Objective: To discuss the effect of EGFR-mTOR signal way in the adaption of cervical carcinoma cell in low glucose and high lactic acid. Methods: Hela cells were cultured in four conditions: normal glucose (NG, glucose 10 mmol/L), low glucose (LG, glucose 3 mmol/L), high lactic acid (HL, lactic acid 2.5 mmol/L) and low glucose and high lactic acid (LGHL, glucose 10 mmol/L, lactic acid 2.5 mmol/L). Growth inhibitory rate of Hela cell was determined by CCK-8; Flow cytometry (FCM) was performed to evaluate the cell cycle; Results: Compared with the rate in NG, the rate in low glucose and high lactic acid was significantly increased (P < 0.01). Compared with the rate in NG, the rate of G1/G0 was increased in HL and in LGHL (P < 0.01, P < 0.01); the rate of G1/G0 in LG didn't have significant difference; the rates of G2/M in HL and in LGHL were decreased, and the G2/M rate in LG was increased, but all of them had no statistically significant. The rates of S were decreased in HL, LG and LGHL (P < 0.05, no statistically significant, P < 0.05). The expression level of EGFR mRNA in Hela was decreased and the level of mTOR mRNA was increased in HL (both had no statistically significant), when compared with the levels in NG. The expression level of EGFR mRNA was decreased (P < 0.05) and the level of mTOR mRNA was a little increased (no statistically significant) in LG; while the EGFR and mTOR expression levels were increased in LGHL (P < 0.05). Conclusion: Low glucose and high lactic acid environment is conducive to Hela cell survival, and can promote the expression of EGFR and mTOR.

Promising Fungicides from Allelochemicals: Synthesis of Umbelliferone Derivatives and Their Structure–Activity Relationships

Umbelliferone was discovered to be an important allelochemical in our previous study, but the contribution of its activity and structure has not yet been revealed. In this study, a series of analogues were synthesized to determine the skeleton of umbelliferone and examine its fungicidal activity. Furthermore, targeted modifications were conducted with three plant parasitic fungi to examine the lead compounds. Among those tested, compounds 2f and 10 were found to show excellent antifungal activity with an inhibitory rate over 80% at 100 ug/mL. The study proves that umbelliferone can be a promising skeleton for fungicides discovery. In addition, the primary structure–activity relationship provides a good guidance for the discovery of novel fungicides based on natural products in the future.

Granulin A Synergizes with Cisplatin to Inhibit the Growth of Human Hepatocellular Carcinoma

Cisplatin is one of the most potent chemotherapy drugs widely used for cancer treatment. However, due to resistance and toxicity, the application of cisplatin for the treatment of hepatocellular carcinoma (HCC) is limited. Our previous study has shown that granulin A (GRN A), an anticancer peptide, is able to interact with enolase1 (ENO1) and inhibit the growth of HCC in vitro. In the present study, we studied the synergistic effect of the combination of cisplatin and GRN A for the inhibitory effect on HCC. An 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and Chou-Talalay approaches revealed that the combination of GRN A and cisplatin displayed potent synergistic effect. The colony formation and cell viability of HCC cells were inhibited significantly in cells treated with the combination of cisplatin and GRN A, compared with cells treated with cisplatin or GRN A alone. Overexpression of ENO1 diminished the synergistic effect of GRN A and cisplatin in HCC cells. The combination of the two drugs exhibited a more obvious inhibitory effect on cancer cell apoptosis, as analyzed by the cytometry flow, mitochondrial membrane potential (MMP) and western blot analysis. An in vivo study confirmed that the combined use of the two drugs displayed more potent antitumor activity compared to mice treated with cisplatin and GRN A alone; the inhibitory rate of tumor growth was 65.46% and 68.94%, respectively, in mice treated with GRN A and cisplatin. However, the inhibitory rate increased to 86.63% in mice treated with the combination of the two drugs. This study provides evidence that the combination of GRN A and cisplatin is able to sensitize the liver cancer to cisplatin, and that targeting ENO1 is a promising approach for enhancing the antitumor activity of cisplatin.

Study on Zeolite X Complexing Dimethyl Potassium

The study took zeolite X as carrier and chitosan as intermediate to compound dimethyl potassium to prepare zeolite X antimicrobial agent by hydrothermal synthesis. The best condition to prepare zeolite X antimicrobial agent is: Mass ratio of zeolite X:Chitosan:dimethyl potassium is 3:1:2, temperature is 40 °C and time is 2 h. Through antibacterial test, we can see that the best inhibitory rate is 78.16%, and release effect significantly enhanced. We studied the structure of zeolite X antimicrobial agent by IR, XRD, SEM, XPS. It can be concluded that: The H on amino-group of chitosan can form hydrogen bonds with O on dimethyl potassium and zeolite X and the hydrogen bonds Play a major role in connecting dimethyl potassium and zeolite X; Free hydroxyl on zeolite X can form hydrogen bonds with O in C-O of chitosan. And it may form hydrogen bonds with O in C=O of dimethyl potassium. And explain the reason of improving of antimicrobial.