scholarly journals Synthesis and Evaluation of Thymol-Based Synthetic Derivatives as Dual-Action Inhibitors against Different Strains of H. pylori and AGS Cell Line

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1829
Author(s):  
Francesca Sisto ◽  
Simone Carradori ◽  
Paolo Guglielmi ◽  
Mattia Spano ◽  
Daniela Secci ◽  
...  
Keyword(s):  
Minimum Inhibitory Concentration ◽  
Inhibitory Concentration ◽  
Current Therapy ◽  
Gastric Diseases ◽  
Ags Cells ◽  
19F Nmr Spectra ◽  
Dual Action ◽  
Human Gastric Adenocarcinoma ◽  
H Pylori ◽  
Different Strains

Following a similar approach on carvacrol-based derivatives, we investigated the synthesis and the microbiological screening against eight strains of H. pylori, and the cytotoxic activity against human gastric adenocarcinoma (AGS) cells of a new series of ether compounds based on the structure of thymol. Structural analysis comprehended elemental analysis and 1H/13C/19F NMR spectra. The analysis of structure–activity relationships within this molecular library of 38 structurally-related compounds reported that some chemical modifications of the OH group of thymol led to broad-spectrum growth inhibition on all isolates. Preferred substitutions were benzyl groups compared to alkyl chains, and the specific presence of functional groups at para position of the benzyl moiety such as 4-CN and 4-Ph endowed the most anti-H. pylori activity toward all the strains with minimum inhibitory concentration (MIC) values up to 4 µg/mL. Poly-substitution on the benzyl ring was not essential. Moreover, several compounds characterized by the lowest minimum inhibitory concentration/minimum bactericidal concentration (MIC/MBC) values against H. pylori were also tested in order to verify a cytotoxic effect against AGS cells with respect to 5-fluorouracil and carvacrol. Three derivatives can be considered as new lead compounds alternative to current therapy to manage H. pylori infection, preventing the occurrence of severe gastric diseases. The present work confirms the possibility to use natural compounds as templates for the medicinal semi-synthesis.

scholarly journals Synthesis and Biological Evaluation of Carvacrol-Based Derivatives as Dual Inhibitors of H. pylori Strains and AGS Cell Proliferation

2020 ◽  
Vol 13 (11) ◽  
pp. 405
Author(s):  
Francesca Sisto ◽  
Simone Carradori ◽  
Paolo Guglielmi ◽  
Carmen Beatrice Traversi ◽  
Mattia Spano ◽  
...  
Keyword(s):  
Parent Compound ◽  
Biological Evaluation ◽  
Ags Cells ◽  
19F Nmr Spectra ◽  
Lead Compounds ◽  
Human Gastric Adenocarcinoma ◽  
Dual Inhibitors ◽  
H Pylori ◽  
Electron Donating Groups ◽  
Synthesis And Biological Evaluation

This study reports on the synthesis, structural assessment, microbiological screening against several strains of H. pylori and antiproliferative activity against human gastric adenocarcinoma (AGS) cells of a large series of carvacrol-based compounds. Structural analyses consisted of elemental analysis, 1H/13C/19F NMR spectra and crystallographic studies. The structure-activity relationships evidenced that among ether derivatives the substitution with specific electron-withdrawing groups (CF3 and NO2) especially in the para position of the benzyl ring led to an improvement of the antimicrobial activity, whereas electron-donating groups on the benzyl ring and ethereal alkyl chains were not tolerated with respect to the parent compound (MIC/MBC = 64/64 µg/mL). Ester derivatives (coumarin-carvacrol hybrids) displayed a slight enhancement of the inhibitory activity up to MIC values of 8–16 µg/mL. The most interesting compounds exhibiting the lowest MIC/MBC activity against H. pylori (among others, compounds 16 and 39 endowed with MIC/MBC values ranging between 2/2 to 32/32 µg/mL against all the evaluated strains) were also assayed for their ability to reduce AGS cell growth with respect to 5-Fluorouracil. Some derivatives can be regarded as new lead compounds able to reduce H. pylori growth and to counteract the proliferation of AGS cells, both contributing to the occurrence of gastric cancer.

scholarly journals The Effects of Sulglycotide on the Adhesion and the Inflammation of Helicobacter Pylori

2020 ◽  
Vol 17 (8) ◽  
pp. 2918
Author(s):  
Ji Yeong Yang ◽  
Pumsoo Kim ◽  
Seok-Hoo Jeong ◽  
Seong Woong Lee ◽  
Yu Sik Myung ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Protein A ◽  
Enzyme Linked Immunosorbent Assay ◽  
Etiologic Factor ◽  
Dilution Method ◽  
Gastric Diseases ◽  
Ags Cells ◽  
Human Gastric Adenocarcinoma ◽  
H Pylori

Helicobacter pylori (H. pylori) is a primary etiologic factor in gastric diseases. Sulglycotide is a glycopeptide derived from pig duodenal mucin. Esterification of its carbohydrate chains with sulfate groups creates a potent gastroprotective agent used to treat various gastric diseases. We investigated the inhibitory effects of sulglycotide on adhesion and inflammation after H. pylori infection in human gastric adenocarcinoma cells (AGS cells). H. pylori reference strain 60190 (ATCC 49503) was cultured on Brucella agar supplemented with 10% bovine serum. Sulgylcotide-mediated growth inhibition of H. pylori was evaluated using the broth dilution method. Inhibition of H. pylori adhesion to AGS cells by sulglycotide was assessed using a urease assay. Effects of sulglycotide on the translocation of virulence factors was measured using western blot to detect cytotoxin-associated protein A (CagA) and vacuolating cytotoxin A (VacA) proteins. Inhibition of IL-8 secretion was measured using enzyme-linked immunosorbent assay (ELISA) to determine the effects of sulglycotide on inflammation. Sulglycotide did not inhibit the growth of H. pylori, however, after six and 12 hours of infection on AGS cells, H. pylori adhesion was significantly inhibited by approximately 60% by various concentrations of sulglycotide. Sulglycotide decreased H. pylori virulence factor (CagA and VacA) translocation to AGS cells and inhibited IL-8 secretion. Sulglycotide inhibited H. pylori adhesion and inflammation after infection of AGS cells in vitro. These results support the use of sulglycotide to treat H. pylori infections.

scholarly journals α-Lipoic Acid Inhibits IL-8 Expression by Activating Nrf2 Signaling in Helicobacter pylori-infected Gastric Epithelial Cells

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2524 ◽  
Author(s):  
Seoyeon Kyung ◽  
Joo Weon Lim ◽  
Hyeyoung Kim
Keyword(s):  
Oxidative Stress ◽  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Lipoic Acid ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Gastric Epithelial Cells ◽  
Gastric Diseases ◽  
Ags Cells ◽  
H Pylori

Helicobacter pylori (H. pylori) causes gastritis and gastric cancers. Oxidative stress is involved in the pathological mechanism of H. pylori-induced gastritis and gastric cancer induction. Therefore, reducing oxidative stress may be beneficial for preventing the development of H. pylori-associated gastric diseases. Nuclear factor erythroid-2-related factor 2 (Nrf2) is a crucial regulator for the expression of antioxidant enzyme heme oxygenase-1 (HO-1), which protects cells from oxidative injury. α-Lipoic acid (α-LA), a naturally occurring dithiol, shows antioxidant and anti-inflammatory effects in various cells. In the present study, we examined the mechanism by which α-LA activates the Nrf2/HO-1 pathway, suppresses the production of pro-inflammatory cytokine interleukine-8 (IL-8), and reduces reactive oxygen species (ROS) in H. pylori-infected AGS cells. α-LA increased the level of phosphorylated and nuclear-translocated Nrf2 by decreasing the amount of Nrf2 sequestered in the cytoplasm by complex formation with Kelch-like ECH1-associated protein 1 (KEAP 1). By using exogenous inhibitors targeting Nrf2 and HO-1, we showed that up-regulation of activated Nrf2 and of HO-1 results in the α-LA-induced suppression of interleukin 8 (IL-8) and ROS. Consumption of α-LA-rich foods may prevent the development of H. pylori-associated gastric diseases by decreasing ROS-mediated IL-8 expression in gastric epithelial cells.

scholarly journals Synthesis and Anti-Saprolegnia Activity of New 2’,4’-Dihydroxydihydrochalcone Derivatives

Antibiotics ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 317
Author(s):  
Enrique Werner ◽  
Iván Montenegro ◽  
Bastian Said ◽  
Patricio Godoy ◽  
Ximena Besoain ◽  
...  
Keyword(s):  
Minimum Inhibitory Concentration ◽  
Cell Membrane ◽  
Inhibitory Concentration ◽  
Addition Compound ◽  
Saprolegnia Parasitica ◽  
Different Strains ◽  
Positive Controls

In the present study, seven 2’,4’-dihydroxydihydrochalcone derivatives (compounds 3–9) were synthesized and their capacity as anti-Saprolegnia agents were evaluated against Saprolegnia parasitica, S. australis, S. diclina. Derivative 9 showed the best activity against the different strains, with minimum inhibitory concentration (MIC) and minimum oomyceticidal concentration (MOC) values between 100–175 μg/mL and 100–200 μg/mL, respectively, compared with bronopol and fluconazole as positive controls. In addition, compound 9 caused damage and disintegration cell membrane of all Saprolegnia strains over the action of commercial controls.

Epithelial and bacterial metalloproteinases and their inhibitors inH. pyloriinfection of human gastric cells

2001 ◽  
Vol 281 (3) ◽  
pp. G823-G832 ◽  
Author(s):  
Monika Göõz ◽  
Pal Göõz ◽  
Adam J. Smolka
Keyword(s):  
Culture Media ◽  
Bacterial Attachment ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Cell Secretion ◽  
Basal Secretion ◽  
Ags Cells ◽  
Host Cell Response ◽  
Caseinolytic Activity ◽  
Human Gastric Adenocarcinoma ◽  
H Pylori

To test the hypothesis that Helicobacter pylori regulates gastric cell secretion of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), culture media from infected and uninfected human gastric adenocarcinoma (AGS) cells were analyzed by zymography, MMP activity assays, and immunoblotting. AGS cells secreted gelatinolytic (prominently 90 kDa) and caseinolytic (110 kDa) activity together with MMP-1, MMP-3, and TIMP-1, TIMP-2, and TIMP-3 isoforms. H. pylori secreted caseinolytic activity (60 kDa), MMP-3-like enzyme activity, and TIMP-3 immunoreactivity. H. pylori infection increased the 110-kDa caseinolytic activity and induced new gelatinolytic (∼35 kDa) and caseinolytic (22 kDa) activities. Infection also increased both basal secretion and activation of MMP-1 and MMP-3, enhanced TIMP-3 secretion, and increased the formation of MMP-3/TIMP-3 complexes. TIMP-1 and TIMP-2 secretion were unchanged. Normal AGS cells showed a pancellular distribution of TIMP-3, with redistribution of immunoreactivity toward sites of bacterial attachment after H. pylori infection. The data indicate that MMP and TIMP secretion by AGS cells is modulated by H. pylori infection and that host MMP-3 and a TIMP-3 homolog expressed by H. pylori mediate at least part of the host cell response to infection.

scholarly journals Immunomodulatory Effects of Psyllium Extract onHelicobacter pyloriInteraction With Gastric Epithelial Cells

2016 ◽  
Vol 21 (4) ◽  
pp. NP18-NP24 ◽  
Author(s):  
Javed Yakoob ◽  
Wasim Jafri ◽  
Malik Hassan Mehmood ◽  
Zaigham Abbas ◽  
Kanwal Tariq
Keyword(s):  
Epithelial Cells ◽  
Messenger Rna ◽  
Cell Culture Supernatant ◽  
Gastric Epithelial Cells ◽  
Ags Cells ◽  
Psyllium Husk ◽  
Human Gastric Adenocarcinoma ◽  
Polymerase Chain ◽  
Anti Inflammatory ◽  
H Pylori

Natural plant product Psyllium has anti-inflammatory activity that can modulate the function of cytokines. We determined the effect of Psyllium husk extract on interleukin (IL)-8 and NF-κB secretion by gastric epithelial cells in response to Helicobacter pylori. Human gastric adenocarcinoma cell line (AGS) cells were pretreated with Psyllium extract in different concentrations before H pylori infection. Cell culture supernatant was analyzed for IL-8 and NF-κB by ELISA. RNA from cells was used for real-time polymerase chain reaction for messenger RNA expression of IL-8. Psyllium extract 5 and 10 μg/mL markedly ( P < .001) lowered basal IL-8 by 64.71% and 74.51%, respectively, and H pylori–stimulated IL-8 was also ( P < .001) lowered by 41.67% and 66.67%, respectively. Psyllium 5 and 10 μg/mL also reduced ( P < .0001) cagA-positive H pylori–induced IL-8 mRNA expression by 42.3% and 67.6%, respectively. Psyllium also reduced ( P = .0001) NF-κB in response to H pylori strains confirming its role as an anti-inflammatory agent.

scholarly journals Outer Membrane Vesicle Production by Helicobacter pylori Represents an Approach for the Delivery of Virulence Factors CagA, VacA and UreA into Human Gastric Adenocarcinoma (AGS) Cells

2021 ◽  
Vol 22 (8) ◽  
pp. 3942
Author(s):  
Yongyu Chew ◽  
Hsin-Yu Chung ◽  
Po-Yi Lin ◽  
Deng-Chyang Wu ◽  
Shau-Ku Huang ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Outer Membrane ◽  
Gastric Adenocarcinoma ◽  
Virulence Factors ◽  
Outer Membrane Vesicles ◽  
Host Cells ◽  
Ags Cells ◽  
Α Subunit ◽  
Human Gastric Adenocarcinoma ◽  
H Pylori

Helicobacter pylori infection is the etiology of several gastric-related diseases including gastric cancer. Cytotoxin associated gene A (CagA), vacuolating cytotoxin A (VacA) and α-subunit of urease (UreA) are three major virulence factors of H. pylori, and each of them has a distinct entry pathway and pathogenic mechanism during bacterial infection. H. pylori can shed outer membrane vesicles (OMVs). Therefore, it would be interesting to explore the production kinetics of H. pylori OMVs and its connection with the entry of key virulence factors into host cells. Here, we isolated OMVs from H. pylori 26,695 strain and characterized their properties and interaction kinetics with human gastric adenocarcinoma (AGS) cells. We found that the generation of OMVs and the presence of CagA, VacA and UreA in OMVs were a lasting event throughout different phases of bacterial growth. H. pylori OMVs entered AGS cells mainly through macropinocytosis/phagocytosis. Furthermore, CagA, VacA and UreA could enter AGS cells via OMVs and the treatment with H. pylori OMVs would cause cell death. Comparison of H. pylori 26,695 and clinical strains suggested that the production and characteristics of OMVs are not only limited to laboratory strains commonly in use, but a general phenomenon to most H. pylori strains.

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