Synthesis, Molecular Modelling and Antibacterial Activity Against Helicobacter pylori of Novel Diflunisal Derivatives as Urease Enzyme Inhibitors

2019 ◽  
Vol 16 (4) ◽  
pp. 392-400 ◽  
Author(s):  
Göknil Pelin Coşkun ◽  
Teodora Djikic ◽  
Sadık Kalaycı ◽  
Kemal Yelekçi ◽  
Fikrettin Şahin ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Antibacterial Activity ◽  
Enzyme Inhibitors ◽  
Binding Modes ◽  
Bacterial Strains ◽  
Urease Enzyme ◽  
H Pylori ◽  
Ulcer Treatment ◽  
Main Factor

Background:The main factor for the prolongation of the ulcer treatment in the gastrointestinal system would be Helicobacter pylori infection, which can possibly lead to gastrointestinal cancer. Triple therapy is the treatment of choice by today's standards. However, observed resistance among the bacterial strains can make the situation even worse. Therefore, there is a need to discover new targeted antibacterial therapy in order to make success in the eradication of H. pylori infections.Methods:The targeted therapy rule is to identify the related macromolecules that are responsible for the survival of the bacteria. Thus, 2-[(2',4'-difluoro-4-hydroxybiphenyl-3-yl)carbonyl]-N- (substituted)hydrazinocarbothioamide (3-13) and 5-(2',4'-difluoro-4-hydroxybiphenyl-3-yl)-4- (substituted)-2,4-dihydro-3H-1,2,4-triazole-3-thiones (14-17) were synthesized and evaluated for antibacterial activity in vitro against H. pylori.Results:All of the tested compounds showed remarkable antibacterial activity compared to the standard drugs (Ornidazole, Metronidazole, Nitrimidazin and Clarithromycin). Compounds 4 and 13 showed activity as 2µg/ml MIC value.Conclusion:In addition, we have investigated binding modes and energy of the compounds 4 and 13 on urease enzyme active by using the molecular docking tools.

scholarly journals In VitroInhibition ofHelicobacter pyloriGrowth by Redox Cycling Phenylaminojuglones

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Julio Benites ◽  
Héctor Toledo ◽  
Felipe Salas ◽  
Angélica Guerrero ◽  
David Rios ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Antibacterial Activity ◽  
Active Compound ◽  
Metabolic Pathways ◽  
Growth Inhibitor ◽  
Growth Inhibitors ◽  
Design Synthesis ◽  
H Pylori

Infection byHelicobacter pyloriincreases 10 times the risk of developing gastric cancer. Juglone, a natural occurring 1,4-naphthoquinone, preventsH. pylorigrowth by interfering with some of its critical metabolic pathways. Here, we report the design, synthesis, andin vitroevaluation of a series of juglone derivatives, namely, 2/3-phenylaminojuglones, as potentialH. pylorigrowth inhibitors. Results show that 5 out of 12 phenylaminojuglones (at 1.5 μg/mL) were 1.5–2.2-fold more active than juglone. Interestingly, most of the phenylaminojuglones (10 out of 12) were 1.1–2.8 fold more active than metronidazole, a knownH. pylorigrowth inhibitor. The most active compound, namely, 2-((3,4,5-trimethoxyphenyl)amino)-5-hydroxynaphthalene-1,4-dione 7, showed significant higher halo of growth inhibitions (HGI = 32.25 mm) to that of juglone and metronidazole (HGI = 14.50 and 11.67 mm). Structural activity relationships of the series suggest that the nature and location of the nitrogen substituents in the juglone scaffold, likely due in part to their redox potential, may influence the antibacterial activity of the series.

scholarly journals In Vitro Activity of a Novel Antimicrobial Agent, TG44, for Treatment of Helicobacter pylori Infection

2006 ◽  
Vol 50 (9) ◽  
pp. 3062-3069 ◽  
Author(s):  
Osamu Kamoda ◽  
Kinsei Anzai ◽  
Jun-ichi Mizoguchi ◽  
Masatoshi Shiojiri ◽  
Toshiharu Yanagi ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Antibacterial Activity ◽  
Bactericidal Activity ◽  
Structural Formula ◽  
Therapeutic Modalities ◽  
Resistant Strains ◽  
H Pylori ◽  
Ph Range ◽  
Drug Resistant Strains

ABSTRACT Due to concerns about the current therapeutic modalities for Helicobacter pylori infection, e.g., the increased emergence of drug-resistant strains and the adverse reactions of drugs currently administered, there is a need to develop an anti-H. pylori agent with higher efficacy and less toxicity. The antibacterial activity of TG44, an anti-H. pylori agent with a novel structural formula, against 54 clinical isolates of H. pylori was examined and compared with those of amoxicillin (AMX), clarithromycin (CLR), and metronidazole (MNZ). Consequently, TG44 inhibited the growth of H. pylori in an MIC range of 0.0625 to 1 μg/ml. The MIC ranges of AMX, CLR, and MNZ were 0.0078 to 8 μg/ml, 0.0156 to 64 μg/ml, and 2 to 128 μg/ml, respectively. The antibacterial activity of TG44 against AMX-, CLR-, and MNZ-resistant strains was nearly comparable to that against drug-susceptible ones. In a pH range of 3 to 7, TG44 at 3.13 to 12.5 μg/ml exhibited potent bactericidal activity against H. pylori in the stationary phase of growth as early as 1 h after treatment began, in contrast to AMX, which showed no bactericidal activity at concentrations of up to 50 μg/ml at the same time point of treatment. TG44 at 25 μg/ml exhibited no antibacterial activity against 13 strains of aerobic bacteria, suggesting that its antibacterial activity against H. pylori is potent and highly specific. The present study indicated that TG44 possesses antibacterial activity which manifests quickly and is potentially useful for eradicating not only the antibiotic-susceptible but also the antibiotic-resistant strains of H. pylori by monotherapy.

scholarly journals Synthesis, In Silico Studies, and Evaluation of Syn and Anti Isomers of N-Substituted Indole-3-carbaldehyde Oxime Derivatives as Urease Inhibitors against Helicobacter pylori

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6658
Author(s):  
Ishani P. Kalatuwawege ◽  
Medha J. Gunaratna ◽  
Dinusha N. Udukala
Keyword(s):  
Helicobacter Pylori ◽  
Gastrointestinal Tract ◽  
In Silico ◽  
Hydroxylamine Hydrochloride ◽  
In Silico Studies ◽  
Urease Enzyme ◽  
Oxime Derivatives ◽  
Urease Inhibitory ◽  
H Pylori

Gastrointestinal tract infection caused by Helicobacter pylori is a common virulent disease found worldwide, and the infection rate is much higher in developing countries than in developed ones. In the pathogenesis of H. pylori in the gastrointestinal tract, the secretion of the urease enzyme plays a major role. Therefore, inhibition of urease is a better approach against H. pylori infection. In the present study, a series of syn and anti isomers of N-substituted indole-3-carbaldehyde oxime derivatives was synthesized via Schiff base reaction of appropriate carbaldehyde derivatives with hydroxylamine hydrochloride. The in vitro urease inhibitory activities of those derivatives were evaluated against that of Macrotyloma uniflorum urease using the modified Berthelot reaction. Out of the tested compounds, compound 8 (IC50 = 0.0516 ± 0.0035 mM) and compound 9 (IC50 = 0.0345 ± 0.0008 mM) were identified as the derivatives with potent urease inhibitory activity with compared to thiourea (IC50 = 0.2387 ± 0.0048 mM). Additionally, in silico studies for all oxime compounds were performed to investigate the binding interactions with the active site of the urease enzyme compared to thiourea. Furthermore, the drug-likeness of the synthesized oxime compounds was also predicted.

scholarly journals Potential of Bacterial Cellulose Chemisorbed with Anti-Metabolites, 3-Bromopyruvate or Sertraline, to Fight against Helicobacter pylori Lawn Biofilm

2020 ◽  
Vol 21 (24) ◽  
pp. 9507 ◽  
Author(s):  
Paweł Krzyżek ◽  
Grażyna Gościniak ◽  
Karol Fijałkowski ◽  
Paweł Migdał ◽  
Mariusz Dziadas ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Antibacterial Activity ◽  
Bacterial Cellulose ◽  
Multidrug Resistant ◽  
Diffusion Method ◽  
Continuous Exposure ◽  
Disk Diffusion Method ◽  
Bacterial Morphology ◽  
H Pylori

Helicobacter pylori is a bacterium known mainly of its ability to cause persistent inflammations of the human stomach, resulting in peptic ulcer diseases and gastric cancers. Continuous exposure of this bacterium to antibiotics has resulted in high detection of multidrug-resistant strains and difficulties in obtaining a therapeutic effect. The purpose of the present study was to determine the usability of bacterial cellulose (BC) chemisorbed with 3-bromopyruvate (3-BP) or sertraline (SER) to act against lawn H. pylori biofilms. The characterization of BC carriers was made using a N2 adsorption/desorption analysis, tensile strength test, and scanning electron microscopy (SEM) observations. Determination of an antimicrobial activity was performed using a modified disk-diffusion method and a self-designed method of testing antibacterial activity against biofilm microbial forms. In addition, bacterial morphology was checked by SEM. It was found that BC disks were characterized by a high cross-linking and shear/stretch resistance. Growth inhibition zones for BC disks chemisorbed with 2 mg of SER or 3-BP were equal to 26.5–27.5 mm and 27–30 mm, respectively. The viability of lawn biofilm H. pylori cells after a 4-h incubation with 2 mg SER or 3-BP chemisorbed on BC disks was ≥4 log lower, suggesting their antibacterial effect. SEM observations showed a number of morphostructural changes in H. pylori cells exposed to these substances. Concluding, SER and 3-BP chemisorbed on BC carriers presented a promising antibacterial activity against biofilm H. pylori cells in in vitro conditions.

scholarly journals Probiotic Lactobacillus spp. act Against Helicobacter pylori-induced Inflammation

2019 ◽  
Vol 8 (1) ◽  
pp. 90 ◽  
Author(s):  
Yi-Hsing Chen ◽  
Wan-Hua Tsai ◽  
Hui-Yu Wu ◽  
Chun-Ya Chen ◽  
Wen-Ling Yeh ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Bacterial Species ◽  
Lactobacillus Rhamnosus ◽  
Gastrointestinal Diseases ◽  
In Vivo Studies ◽  
Bacterial Strains ◽  
H Pylori ◽  
Lactobacillus Spp

The bacterial species, Helicobacter pylori, is associated with several gastrointestinal diseases, and poses serious health threats owing to its resistance to antibiotics. Lactobacillus spp., on the other hand, possess probiotic activities that have beneficial effects in humans. However, the mechanisms by which Lactobacillus spp. harbor favorable functions and act against H. pylori infection remain to be explored. The aim of this study was to investigate the ability of bacterial strains, Lactobacillus rhamnosus and Lactobacillus acidophilus, termed GMNL-74 and GMNL-185, respectively, to inhibit H. pylori growth and inflammation. Our results showed that GMNL-74 and GMNL-185 possess potent antimicrobial activity against multidrug resistant (MDR)-H. pylori. In addition, an in vitro cell-based model revealed that the inhibition of H. pylori adhesion and invasion of gastric epithelial cells and interleukin-8 production were significantly decreased by treatment with both the Lactobacillus strains. In vivo studies demonstrated that colonization of H. pylori and induced inflammation in the mouse stomach were also alleviated by these Lactobacillus strains. Furthermore, the abundance of beneficial gut bacteria, including Bifidobacterium spp. and Akkermansia muciniphilia, were significantly increased in H. pylori-infected mice treated with GMNL-74 and GMNL-185. These results demonstrate that Lactobacillus spp. ameliorate H. pylori-induced inflammation and supports beneficial gut specific bacteria that act against H. pylori infection.

scholarly journals In vitro activities of new quinolones against Helicobacter pylori.

1997 ◽  
Vol 41 (12) ◽  
pp. 2790-2792 ◽  
Author(s):  
M Carbone ◽  
M T Fera ◽  
V Cecchetti ◽  
O Tabarrini ◽  
E Losi ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Antibacterial Activity ◽  
Fluorine Atom ◽  
New Class ◽  
New Quinolones ◽  
In Vitro Antibacterial Activity ◽  
Inhibitory Activities ◽  
H Pylori

Compounds belonging to a new class of quinolones in which the fundamental C-6 fluorine atom was replaced were evaluated for in vitro antibacterial activity against 32 Helicobacter pylori strains. Since these substitutions resulted in higher inhibitory activities, these new desfluoroquinolones may be useful in eradicating H. pylori infections.

scholarly journals In Vitro Screening Potential Antibacterial Properties of the Greek Oregano Honey against Clinical Isolates of Helicobacter pylori

Foods ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1568
Author(s):  
Chrysoula (Chrysa) Voidarou ◽  
Georgios Rozos ◽  
Athanasios Alexopoulos ◽  
Stavros Plessas ◽  
Ioanna Mantzourani ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Antibacterial Properties ◽  
Gastric Ulcers ◽  
Mountainous Area ◽  
Bacterial Strains ◽  
Gastric Diseases ◽  
Popular Medicine ◽  
Traditional Remedy ◽  
H Pylori

Oregano honey is an exceedingly rare and distinct product, not commercially available, produced by bees bred in oregano fields of alpine altitudes at the mountainous area of Epirus, Greece. In ethnic popular medicine, this product is used as a therapeutic in various gastric diseases. To test this hypothesis, 14 strains of Helicobacter pylori (H. pylori), 6 isolated from gastric ulcers and 8 from cases of clinical gastritis, were employed in the present study. The above bacterial strains were exposed to various concentrations (75% v/v, 50% v/v, 25% v/v, 12.5% v/v, and 6% v/v) of 50 oregano honey samples by using the agar well method and the inhibition zones observed around each well were recorded. Although the inhibitory zones of the H. pylori isolated from the gastric ulcers were wide enough (0–34 mm), those strains, in general, appeared more resistant than the other eight (0–58 mm). The same result was observed when the same strains were tested against six antibiotics used in clinical practice. Extracts of oregano honey were prepared by extraction with four different organic solvents. N-hexane and chloroform extracts had the most potent antibacterial action. Finally, pure oregano honey and diethyl ether extracts of honey showed significant inhibitory activity against urease secreted by the pathogen. These results strongly indicate the susceptibility of H. pylori strains to the oregano honey by more than one mode of action. Consequently, this variety of honey seems to have potential therapeutic properties against gastric ulcers and gastritis, thus explaining the preference of the locals towards this traditional remedy.

The rod-to-coccoid body transformation in cultures of Helicobacter pylori

1990 ◽  
Vol 48 (3) ◽  
pp. 626-627
Author(s):  
A. R. Crooker ◽  
W. G. Kraft ◽  
T. L. Beard ◽  
M. C. Myers
Keyword(s):  
Helicobacter Pylori ◽  
Growth Cycle ◽  
Negative Bacterium ◽  
Body Formation ◽  
Coccoid Form ◽  
Spiral Form ◽  
Prolonged Culture ◽  
H Pylori ◽  
Upper Gastrointestinal

Helicobacter pylori is a microaerophilic, gram-negative bacterium found in the upper gastrointestinal tract of humans. There is strong evidence that H. pylori is important in the etiology of gastritis; the bacterium may also be a major predisposing cause of peptic ulceration. On the gastric mucosa, the organism exists as a spiral form with one to seven sheathed flagella at one (usually) or both poles. Short spirals were seen in the first successful culture of the organism in 1983. In 1984, Marshall and Warren reported a coccoid form in older cultures. Since that time, other workers have observed rod and coccal forms in vitro; coccoid forms predominate in cultures 3-7 days old. We sought to examine the growth cycle of H. pylori in prolonged culture and the mode of coccoid body formation.

Synthesis and In Vitro Enzymatic Studies of New 3-Aryldiazenyl Indoles as Promising Helicobacter pylori IMPDH Inhibitors

2019 ◽  
Vol 19 (5) ◽  
pp. 376-382 ◽  
Author(s):  
Sachin Jangra ◽  
Gayathri Purushothaman ◽  
Kapil Juvale ◽  
Srimadhavi Ravi ◽  
Aishwarya Menon ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Bacterial Infections ◽  
Immunosuppressive Drugs ◽  
Multi Drug Resistance ◽  
Metabolic Enzyme ◽  
World Population ◽  
Inhibitor Molecule ◽  
Nucleotide Synthesis ◽  
H Pylori

Background & Objective:Helicobacter pylori infection is one of the primary causes of peptic ulcer followed by gastric cancer in the world population. Due to increased occurrences of multi-drug resistance to the currently available antibiotics, there is an urgent need for a new class of drugs against H. pylori. Inosine 5′-monophosphate dehydrogenase (IMPDH), a metabolic enzyme plays a significant role in cell proliferation and cell growth. It catalyses guanine nucleotide synthesis. IMPDH enzyme has been exploited as a target for antiviral, anticancer and immunosuppressive drugs. Recently, bacterial IMPDH has been studied as a potential target for treating bacterial infections. Differences in the structural and kinetic parameters of the eukaryotic and prokaryotic IMPDH make it possible to target bacterial enzyme selectively.Methods:In the current work, we have synthesised and studied the effect of substituted 3-aryldiazenyl indoles on Helicobacter pylori IMPDH (HpIMPDH) activity. The synthesised molecules were examined for their inhibitory potential against recombinant HpIMPDH.Results:In this study, compounds 1 and 2 were found to be the most potent inhibitors amongst the database with IC50 of 0.8 ± 0.02µM and 1 ± 0.03 µM, respectively.Conclusion:When compared to the most potent known HpIMPDH inhibitor molecule C91, 1 was only four-fold less potent and can be a good lead for further development of selective and potent inhibitors of HpIMPDH.

scholarly journals Nutrient Deficiency Promotes the Entry of Helicobacter pylori Cells into Candida Yeast Cells

Biology ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 426
Author(s):  
Kimberly Sánchez-Alonzo ◽  
Fabiola Silva-Mieres ◽  
Luciano Arellano-Arriagada ◽  
Cristian Parra-Sepúlveda ◽  
Humberto Bernasconi ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Nutrient Deficiency ◽  
Gastric Epithelium ◽  
Yeast Cells ◽  
Nutrient Concentrations ◽  
Fetal Bovine ◽  
H Pylori ◽  
Pcr Techniques ◽  
Strain Dependent

Helicobacter pylori, a Gram-negative bacterium, has as a natural niche the human gastric epithelium. This pathogen has been reported to enter into Candida yeast cells; however, factors triggering this endosymbiotic relationship remain unknown. The aim of this work was to evaluate in vitro if variations in nutrient concentration in the cultured medium trigger the internalization of H. pylori within Candida cells. We used H. pylori–Candida co-cultures in Brucella broth supplemented with 1%, 5% or 20% fetal bovine serum or in saline solution. Intra-yeast bacteria-like bodies (BLBs) were observed using optical microscopy, while intra-yeast BLBs were identified as H. pylori using FISH and PCR techniques. Intra-yeast H. pylori (BLBs) viability was confirmed using the LIVE/DEAD BacLight Bacterial Viability kit. Intra-yeast H. pylori was present in all combinations of bacteria–yeast strains co-cultured. However, the percentages of yeast cells harboring bacteria (Y-BLBs) varied according to nutrient concentrations and also were strain-dependent. In conclusion, reduced nutrients stresses H. pylori, promoting its entry into Candida cells. The starvation of both H. pylori and Candida strains reduced the percentages of Y-BLBs, suggesting that starving yeast cells may be less capable of harboring stressed H. pylori cells. Moreover, the endosymbiotic relationship between H. pylori and Candida is dependent on the strains co-cultured.

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