Lead Molecules for Targeted Urease Inhibition: An Updated Review from 2010 -2018

2019 ◽  
Vol 20 (12) ◽  
pp. 1158-1188 ◽  
Author(s):  
Ritu Kataria ◽  
Anurag Khatkar
Keyword(s):  
Enzyme Mechanism ◽  
Bacillus Pasteurii ◽  
Pathological Conditions ◽  
Current Review ◽  
Current Topic ◽  
Wide Range ◽  
Mechanism Of Catalysis ◽  
Urease Inhibitory ◽  
H Pylori ◽  
Hydrolysis Of

The field of enzyme inhibition is a tremendous and quickly growing territory of research. Urease a nickel containing metalloenzyme found in bacteria, algae, fungi, and plants brings hydrolysis of urea and plays important role in environmental nitrogen cycle. Apart from this it was found to be responsible for many pathological conditions due to its presence in many microorganisms such as H. Pylori, a ureolytic bacteria having urease which elevates pH of gastric medium by hydrolyzing urea present in alimentary canal and help the bacteria to colonize and spread infection. Due to the infections caused by the various bacterial ureases such as Bacillus pasteurii, Brucella abortus, H. pylori, H. mustelae, Klebsiella aerogenes, Klebsiella tuberculosis, Mycobacterium tuberculosis, Pseudomonas putida, Sporosarcina pasteurii and Yersinia enterocolitica, it has been the current topic of today’s research. About a wide range of compounds from the exhaustive literature survey has been discussed in this review which is enveloped into two expansive classes, as Inhibitors from synthetic origin and Inhibitors from natural origin. Moreover active site details of enzyme, mechanism of catalysis of substrate by enzyme, uses of plant urease and its pathogenic behavior has been included in the current review. So, overall, this review article diagrams the current landscape of the developments in the improvements in the thriving field of urease inhibitory movement in medicinal chemistry from year 2010 to 2018, with an emphasis on mechanism of action of inhibitors that may be used for more development of recent and strong urease inhibitors and open up new doors for assist examinations in a standout amongst the most lively and promising regions of research.

scholarly journals Studies on the mechanism of sheep liver cytosolic aldehyde dehydrogenase. The effect of pH on the aldehyde binding reactions and a re-examination of the problem of the site of proton release in the mechanism

1986 ◽  
Vol 238 (1) ◽  
pp. 75-82 ◽  
Author(s):  
F M Dickinson
Keyword(s):  
Initial Rate ◽  
Substrate Inhibition ◽  
Cysteine Residue ◽  
Stopped Flow ◽  
Proton Release ◽  
Fluorescence Studies ◽  
Wide Range ◽  
Mechanism Of Catalysis ◽  
Hydrolysis Of ◽  
Enzyme Species

Initial-rate measurements and stopped-flow spectrophotometric experiments over a wide range of pH implicate an enzyme group of pKa approximately 6.6 affecting the aldehyde binding reactions. It is possible, though not proved, that the group involved is the cysteine residue involved in catalysis. Stopped-flow fluorescence studies show that a group of pKa greater than 8.5 facilitates hydrolysis of the NADH-containing acyl-enzyme species. The identity of this group is quite unknown. Studies with 4-nitrobenzaldehyde show that this substrate gives marked substrate inhibition at quite low (less than 20 microM) concentrations. The mechanism of catalysis seems to be the same as for propionaldehyde oxidation. It is argued that proton release occurs with both substrates on hydrolysis of the NADH-containing acyl-enzyme and not before hydride transfer, as has been previously suggested [Bennett, Buckley & Blackwell (1982) Biochemistry 21, 4407-4413].

Synthesis, Antioxidant and Antiurease Activities of Some New 5,6- dichloro-2-(4-fluorobenzyl)-1H-benzimidazole Derivatives Containing Furan, Oxadiazole, Triazole and Thiadiazole Moieties

2019 ◽  
Vol 16 (8) ◽  
pp. 939-947
Author(s):  
Hakan Bektas ◽  
Canan Albay ◽  
Emre Menteşe ◽  
Bahar Bilgin Sokmen ◽  
Zafer Kurt ◽  
...  
Keyword(s):  
Biological Activities ◽  
Benzimidazole Derivatives ◽  
Wide Range ◽  
Ic50 Values ◽  
Urease Inhibitory

Background:Benzimidazoles and its derivatives have been attracting interest for many years because of their biological activities. Benzimidazoles containing different heterocyclic moieties have wide range of biological activities such as antimicrobial, antioxidant, anticancer, antiviral, etc.Methods:In this study, some benzimidazole derivatives containing furan, oxadiazole, triazole and thiadiazole moieties have been synthesized and then evaluated for their antioxidant and antiurease activities.Results:The results showed that all the tested benzimidazoles indicated remarkable urease inhibitory potentials with IC50 values ranging between 0.303±0.03 to 0.591±0.08 µM.Conclusion:In conclusion, synthesized benzimidazole derivatives showed good antioxidant and antiurease activities. Heterocyclic groups on benzimidazole nucleus enhance the activities.

scholarly journals The Hsp60 Protein of Helicobacter Pylori Exhibits Chaperone and ATPase Activities at Elevated Temperatures

BioChem ◽  
2021 ◽  
Vol 1 (1) ◽  
pp. 19-25
Author(s):  
Jose A. Mendoza ◽  
Julian L. Ignacio ◽  
Christopher M. Buckley
Keyword(s):  
Helicobacter Pylori ◽  
Heat Stress ◽  
Molecular Chaperone ◽  
Elevated Temperatures ◽  
Citrate Synthase ◽  
Gastric Epithelium ◽  
Acidic Conditions ◽  
H Pylori ◽  
Induced Aggregation ◽  
Hydrolysis Of

The heat-shock protein, Hsp60, is one of the most abundant proteins in Helicobacter pylori. Given its sequence homology to the Escherichia coli Hsp60 or GroEL, Hsp60 from H. pylori would be expected to function as a molecular chaperone in this organism. H. pylori is a type of bacteria that grows on the gastric epithelium, where the pH can fluctuate between neutral and 4.5, and the intracellular pH can be as low as 5.0. We previously showed that Hsp60 functions as a chaperone under acidic conditions. However, no reports have been made on the ability of Hsp60 to function as a molecular chaperone under other stressful conditions, such as heat stress or elevated temperatures. We report here that Hsp60 could suppress the heat-induced aggregation of the enzymes rhodanese, malate dehydrogenase, citrate synthase, and lactate dehydrogenase. Moreover, Hsp60 was found to have a potassium and magnesium-dependent ATPase activity that was stimulated at elevated temperatures. Although, Hsp60 was found to bind GTP, the hydrolysis of this nucleotide could not be observed. Our results show that Hsp60 from H. pylori can function as a molecular chaperone under conditions of heat stress.

scholarly journals When the Balance Tips: Dysregulation of Mitochondrial Dynamics as a Culprit in Disease

2021 ◽  
Vol 22 (9) ◽  
pp. 4617
Author(s):  
Styliana Kyriakoudi ◽  
Anthi Drousiotou ◽  
Petros P. Petrou
Keyword(s):  
Insulin Resistance ◽  
Mitochondrial Function ◽  
Human Disease ◽  
Molecular Mechanisms ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fusion ◽  
Mitochondrial Morphology ◽  
Disease Development ◽  
Pathological Conditions ◽  
Wide Range

Mitochondria are dynamic organelles, the morphology of which is tightly linked to their functions. The interplay between the coordinated events of fusion and fission that are collectively described as mitochondrial dynamics regulates mitochondrial morphology and adjusts mitochondrial function. Over the last few years, accruing evidence established a connection between dysregulated mitochondrial dynamics and disease development and progression. Defects in key components of the machinery mediating mitochondrial fusion and fission have been linked to a wide range of pathological conditions, such as insulin resistance and obesity, neurodegenerative diseases and cancer. Here, we provide an update on the molecular mechanisms promoting mitochondrial fusion and fission in mammals and discuss the emerging association of disturbed mitochondrial dynamics with human disease.

scholarly journals Role of Thioredoxin-Interacting Protein in Diseases and Its Therapeutic Outlook

2021 ◽  
Vol 22 (5) ◽  
pp. 2754
Author(s):  
Naila Qayyum ◽  
Muhammad Haseeb ◽  
Moon Suk Kim ◽  
Sangdun Choi
Keyword(s):  
Interacting Protein ◽  
Thioredoxin Interacting Protein ◽  
Signaling Complex ◽  
Current Review ◽  
Wide Range ◽  
Range Of Functions ◽  
Species Production ◽  
And Oxidative Stress ◽  
Significant Attention

Thioredoxin-interacting protein (TXNIP), widely known as thioredoxin-binding protein 2 (TBP2), is a major binding mediator in the thioredoxin (TXN) antioxidant system, which involves a reduction-oxidation (redox) signaling complex and is pivotal for the pathophysiology of some diseases. TXNIP increases reactive oxygen species production and oxidative stress and thereby contributes to apoptosis. Recent studies indicate an evolving role of TXNIP in the pathogenesis of complex diseases such as metabolic disorders, neurological disorders, and inflammatory illnesses. In addition, TXNIP has gained significant attention due to its wide range of functions in energy metabolism, insulin sensitivity, improved insulin secretion, and also in the regulation of glucose and tumor suppressor activities in various cancers. This review aims to highlight the roles of TXNIP in the field of diabetology, neurodegenerative diseases, and inflammation. TXNIP is found to be a promising novel therapeutic target in the current review, not only in the aforementioned diseases but also in prolonged microvascular and macrovascular diseases. Therefore, TXNIP inhibitors hold promise for preventing the growing incidence of complications in relevant diseases.

scholarly journals In Vitro Incorporation of Helicobacter pylori into Candida albicans Caused by Acidic pH Stress

Pathogens ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 489 ◽  
Author(s):  
Kimberly Sánchez-Alonzo ◽  
Cristian Parra-Sepúlveda ◽  
Samuel Vega ◽  
Humberto Bernasconi ◽  
Víctor L. Campos ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Candida Albicans ◽  
Pcr Amplification ◽  
Growth Curves ◽  
Acidic Ph ◽  
Ph Values ◽  
16S Gene ◽  
Wide Range ◽  
H Pylori

Yeasts can adapt to a wide range of pH fluctuations (2 to 10), while Helicobacter pylori, a facultative intracellular bacterium, can adapt to a range from pH 6 to 8. This work analyzed if H. pylori J99 can protect itself from acidic pH by entering into Candida albicans ATCC 90028. Growth curves were determined for H. pylori and C. albicans at pH 3, 4, and 7. Both microorganisms were co-incubated at the same pH values, and the presence of intra-yeast bacteria was evaluated. Intra-yeast bacteria-like bodies were detected using wet mounting, and intra-yeast binding of anti-H. pylori antibodies was detected using immunofluorescence. The presence of the H. pylori rDNA 16S gene in total DNA from yeasts was demonstrated after PCR amplification. H. pylori showed larger death percentages at pH 3 and 4 than at pH 7. On the contrary, the viability of the yeast was not affected by any of the pHs evaluated. H. pylori entered into C. albicans at all the pH values assayed but to a greater extent at unfavorable pH values (pH 3 or 4, p = 0.014 and p = 0.001, respectively). In conclusion, it is possible to suggest that H. pylori can shelter itself within C. albicans under unfavorable pH conditions.

Lateral skull base surgery: a complicated pursuit?

2007 ◽  
Vol 122 (3) ◽  
pp. 221-229
Author(s):  
V C Cousins
Keyword(s):  
Skull Base ◽  
Skull Base Surgery ◽  
Treatment Modalities ◽  
Published Data ◽  
Know How ◽  
Team Assessment ◽  
Pathological Conditions ◽  
Lateral Skull Base ◽  
Wide Range ◽  
Multi Disciplinary Team

AbstractThe management of lesions of the lateral skull base is a highly sophisticated branch of surgery generally performed by otolaryngology–head and neck surgeons as part of a multi-disciplinary team. Assessment of patients with diseases affecting the lateral skull base can be complex, as can the application of the various treatment modalities and the management of the expected and unexpected side effects of that treatment.A wide range of pathological conditions occur in the lateral skull base. Many operations and procedures have been described for dealing with them. There is not necessarily one correct solution to the management of any particular problem in the skull base, with multiple factors to be considered in planning and intervention.As surgeons, we need to know how our own results and outcomes compare with pooled, published data concerning the implications and complications occurring as a result of intervention, in order to better advise our patients on their management.

scholarly journals Phosphatase synthesis in Klebsiella (Aerobacter) aerogenes growing in continuous culture

1972 ◽  
Vol 127 (1) ◽  
pp. 87-96 ◽  
Author(s):  
P. G. Bolton ◽  
A. C. R. Dean
Keyword(s):  
Alkaline Phosphatase ◽  
Acid Phosphatase ◽  
Continuous Culture ◽  
Activity Profile ◽  
Glucose Effect ◽  
Ph Values ◽  
Nitrophenyl Phosphate ◽  
Wide Range ◽  
Rate Of Hydrolysis ◽  
Hydrolysis Of

1. Phosphatase synthesis was studied in Klebsiella aerogenes grown in a wide range of continuous-culture systems. 2. Maximum acid phosphatase synthesis was associated with nutrient-limited, particularly carbohydrate-limited, growth at a relatively low rate, glucose-limited cells exhibiting the highest activity. Compared with glucose as the carbon-limiting growth material, other sugars not only altered the activity but also changed the pH–activity profile of the enzyme(s). 3. The affinity of the acid phosphatase in glucose-limited cells towards p-nitrophenyl phosphate (Km 0.25–0.43mm) was similar to that of staphylococcal acid phosphatase but was ten times greater than that of the Escherichia coli enzyme. 4. PO43−-limitation derepressed alkaline phosphatase synthesis but the amounts of activity were largely independent of the carbon source used for growth. 5. The enzymes were further differentiated by the effect of adding inhibitors (F−, PO43−) and sugars to the reaction mixture during the assays. In particular, it was shown that adding glucose, but not other sugars, stimulated the rate of hydrolysis of p-nitrophenyl phosphate by the acid phosphatase in carbohydrate-limited cells at low pH values (<4.6) but inhibited it at high pH values (>4.6). Alkaline phosphatase activity was unaffected. 6. The function of phosphatases in general is discussed and possible mechanisms for the glucose effect are outlined.

Some aspects of hemostasis in the tactics of the ophthalmologist. Literature review

2021 ◽  
pp. 265-270
Author(s):  
O.M. Stanishevskaya ◽  
◽  
M.A. Safronova ◽  
G.V. Bratko ◽  
I.Y. Efremova ◽  
...  
Keyword(s):  
Open Angle Glaucoma ◽  
Vascular Diseases ◽  
Laboratory Diagnosis ◽  
The Body ◽  
Vascular Pathology ◽  
Treatment Result ◽  
Important Place ◽  
Correct Orientation ◽  
Pathological Conditions ◽  
Wide Range

Disorders of hemostasis occupy an important place in the structure of vascular diseases and are one of the most frequent pathological conditions encountered in practical medicine. The hemostasis system is naturally the most vulnerable system of the body. Violations of its balance are found in a wide variety of physiological and pathological conditions of the body. It is not uncommon for the first debut of decompensation to lead to an ophthalmologist. In the practice of an ophthalmologist, there are diseases when it is necessary to pay close attention to thrombophilic conditions. Changes in the hemostatic system, affect a wide range of vascular diseases of the eyeball. Recognition of the type of thrombophilia and its timely laboratory diagnosis in patients with vascular diseases of the retina and optic nerve are important in achieving the best treatment results. Multidisciplinary approach to the treatment of vascular diseases of the eyeball and modern diagnostics, including the study of hemostasis, is necessary and relevant to achieve the best clinical and functional treatment result. Timely and correct orientation of patients in vascular pathology is extremely important due to the fact that concomitant systemic pathology can aggravate the course of the disease, therefore, the choice of treatment tactics for this category of patients should be carried out in conjunction with a therapist, cardiologist, hematologist and endocrinologist. Key words: hemostasis, thrombosis CVS, diabet, primary open-angle glaucoma thrombodynamica, cardiovascular pathology.

The impact of SARS-Cov-2 on the Nervous system and Mental Health

2021 ◽  
Vol 19 ◽  
Author(s):  
Mohamed Said Boulkrane ◽  
Victoria Ilina ◽  
Roman Melchakov ◽  
Mikhail Arisov ◽  
Julia Fedotova ◽  
...  
Keyword(s):  
Mental Health ◽  
Respiratory Illness ◽  
World Health ◽  
Current Review ◽  
Wide Range ◽  
Serious Disease ◽  
Health Organization ◽  
The Impact ◽  
The Brain ◽  
Severe Acute Respiratory Illness

: The World Health Organization declared the pandemic situation caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) in March 2020, but the detailed pathophysiological mechanisms of Coronavirus disease 2019 (COVID-19) are not yet completely understood. Therefore, to date, few therapeutic options are available for patients with mild-moderate or serious disease. In addition to systemic and respiratory symptoms, several reports have documented various neurological symptoms and impairments of mental health. The current review aims to provide the available evidence about the effects of SARS-CoV-2 infection on mental health. The present data suggest that SARS-CoV-2 produces a wide range of impairments and disorders of the brain. However, a limited number of studies investigated the neuroinvasive potential of SARS-CoV-2. Although the main features and outcomes of COVID-19 are linked to severe acute respiratory illness. The possible damages on the brain should be considered, too.

Sign in / Sign up

Export Citation Format

Share Document