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Journal of Comparative Effectiveness... Aug 202320 mg of vonoprazan (VPZ20) is recommended in most countries to treat erosive esophagitis (EE). Whether other doses of vonoprazan, such as 5 mg (VPZ5), 10 mg... (Meta-Analysis)
Meta-Analysis Review
20 mg of vonoprazan (VPZ20) is recommended in most countries to treat erosive esophagitis (EE). Whether other doses of vonoprazan, such as 5 mg (VPZ5), 10 mg (VPZ10), 20 mg (VPZ20), and 40 mg (VPZ40) are more effective is unknown. Three databases were electronically searched to identify studies published before November 2021. Network meta-analysis was performed using STATA 14.0. VPZ20 and VPZ40 were comparable to PPI, VPZ5 and VPZ10 in 4- and 8-week healing rates, and this was also detected in patients with refractory EE. All regimens resulted in similar treatment-emergent adverse events (TEAEs). However, VPZ40 ranked first for healing rate and TEAEs; however, VPZ20 ranked worst for TEAEs. Different doses of VPZ are comparable in efficacy and safety, but VPZ40 may be best in both effectiveness and safety.
Topics: Humans; Proton Pump Inhibitors; Esophagitis, Peptic; Network Meta-Analysis; Pyrroles; Peptic Ulcer; Treatment Outcome
PubMed: 37470274
DOI: 10.57264/cer-2022-0165 -
Analytica Chimica Acta Aug 2022Electronic tongues (e-tongues) are analytical technologies that mimic the biological tongues which are non-specific, low-selective, and cross-sensitive taste systems.... (Review)
Review
Electronic tongues (e-tongues) are analytical technologies that mimic the biological tongues which are non-specific, low-selective, and cross-sensitive taste systems. The e-tongues consist of an array of sensors, being able to produce electrical signals that correspond to particular chemical compositions of a sample solution. The performance and efficiency of e-tongues have been optimized for many years via the development of novel materials and technologies. Various conjugated polymers (CPs) have been used in e-tongues over the past decades thanks to their fascinating electrical properties and wide-ranging chemistries. In most studies, CPs such as polypyrrole (PPy), polyaniline (PANI), polythiophene (PT), and poly(3,4-ethylenedioxythiophene) (PEDOT), have drawn considerable interest in e-tongues because of their controllable electrical properties, relatively facile and cost-effective preparation, and good environmental stability that can significantly enhance their versatility, compared to other types of e-tongues. This review article reports major conjugated polymer-based e-tongues (CPETs) that have been studied with these aforementioned CPs over the last two decades.
Topics: Electronic Nose; Polymers; Pyrroles
PubMed: 35934355
DOI: 10.1016/j.aca.2022.340114 -
International Journal of Molecular... Feb 2023Redox imbalance or oxidative stress that results from both environmental and genetic factors is observed in patients with schizophrenia. Therefore, identifying markers... (Review)
Review
Redox imbalance or oxidative stress that results from both environmental and genetic factors is observed in patients with schizophrenia. Therefore, identifying markers of oxidative stress in the early stages of psychosis and using antioxidant treatments as an adjuvant to antipsychotics has important implications. The reaction of -,-dimethylaminobenzaldehyde (DMAB) with pyrrole moieties has been well studied for well over a century for use as a marker of oxidative stress dysregulation. Throughout this time, pyrroles have been investigated with varying veracity in urine extracts to identify elevated levels in patients diagnosed with schizophrenia. Since the 1960's, various claims have been made with respect to what causes the colour change when DMAB is added to urine extracts. Whilst the substances from this reaction have not been fully elucidated, an objective look at most studies indicates that urobilinogen is likely to be one them. Urobilinogen has also been identified as a major interferent in our results. Both pyrroles and urobilinogen condense the DMAB reaction system (form condensation products) and are quite different. The urobilinogen detected in urine forms when gut microflora chemically reduces the bilirubin content of bile acids. In comparison, evidence suggests that the pyrrole fraction originates from the fragmentation of regulatory haem by reactive oxygen species (ROS) such as hydrogen peroxide and super and nitrous oxides. Clinical studies in our laboratories have established that pyrroles as a urine biomarker have specificity in detecting schizophrenia; however, caution must be applied as the readings are subject to interference by other DMAB active compounds that are present, such as urobilinogen. This review highlights the initial chemistry in isolating pyrroles and provides recommendations for standardised laboratory testing to ensure pyrroles are correctly measured and distinguished from other by-products.
Topics: Humans; Pyrroles; Urobilinogen; Bilirubin; Oxidation-Reduction; Oxidative Stress
PubMed: 36769035
DOI: 10.3390/ijms24032712 -
Marine Drugs Sep 2021Nitrogen heterocycles are essential parts of the chemical machinery of life and often reveal intriguing structures. They are not only widespread in terrestrial habitats... (Review)
Review
Nitrogen heterocycles are essential parts of the chemical machinery of life and often reveal intriguing structures. They are not only widespread in terrestrial habitats but can also frequently be found as natural products in the marine environment. This review highlights the important class of marine pyrrole alkaloids, well-known for their diverse biological activities. A broad overview of the marine pyrrole alkaloids with a focus on their isolation, biological activities, chemical synthesis, and derivatization covering the decade from 2010 to 2020 is provided. With relevant structural subclasses categorized, this review shall provide a clear and timely synopsis of this area.
Topics: Alkaloids; Animals; Aquatic Organisms; Pyrroles; Structure-Activity Relationship
PubMed: 34564176
DOI: 10.3390/md19090514 -
European Journal of Medicinal Chemistry Dec 2020The discovery of novel synthetic compounds with drug-like properties is an ongoing challenge in medicinal chemistry. Natural products have inspired the synthesis of... (Review)
Review
The discovery of novel synthetic compounds with drug-like properties is an ongoing challenge in medicinal chemistry. Natural products have inspired the synthesis of compounds for pharmaceutical application, most of which are based on N-heterocyclic motifs. Among these, the pyrrole ring is one of the most explored heterocycles in drug discovery programs for several therapeutic areas, confirmed by the high number of pyrrole-based drugs reaching the market. In the present review, we focused on pyrrole and its hetero-fused derivatives with anticancer, antimicrobial, and antiviral activities, reported in the literature between 2015 and 2019, for which a specific target was identified, being responsible for their biological activity. It emerges that the powerful pharmaceutical and pharmacological features provided by the pyrrole nucleus as pharmacophore unit of many drugs are still recognized by medicinal chemists.
Topics: Anti-Infective Agents; Antineoplastic Agents; Antiviral Agents; Drug Design; Humans; Molecular Targeted Therapy; Pyrroles
PubMed: 32916311
DOI: 10.1016/j.ejmech.2020.112783 -
Organic Letters Oct 2020Using a commercially available, inexpensive, and abundant copper catalyst system, an efficient α-functionalization of nitroalkanes with propargyl bromides is now...
Using a commercially available, inexpensive, and abundant copper catalyst system, an efficient α-functionalization of nitroalkanes with propargyl bromides is now established. This mild and robust method is highly functional group tolerant and provides straightforward access to complex secondary and tertiary homopropargylic nitroalkanes. Moreover, the utility of these α-propargylated nitroalkanes is demonstrated through downstream functionalization to biologically relevant, five-membered -heterocycles such as pyrroles and 2-pyrrolines.
Topics: Catalysis; Copper; Molecular Structure; Nitro Compounds; Pyrroles
PubMed: 33006901
DOI: 10.1021/acs.orglett.0c03061 -
Nature Medicine Dec 2021Advanced systemic mastocytosis (AdvSM) is a rare hematologic neoplasm driven by the KIT D816V mutation and associated with poor survival. This phase 1 study (...
Advanced systemic mastocytosis (AdvSM) is a rare hematologic neoplasm driven by the KIT D816V mutation and associated with poor survival. This phase 1 study ( NCT02561988 ) evaluated avapritinib (BLU-285), a selective KIT D816V inhibitor, in patients with AdvSM. The primary endpoints were the maximum tolerated dose, recommended phase 2 dose and safety of avapritinib. Secondary endpoints included overall response rate and changes in measures of mast cell burden. Avapritinib was evaluated at doses of 30-400 mg once daily in 86 patients, 69 with centrally confirmed AdvSM. Maximum tolerated dose was not reached, and 200 mg and 300 mg daily were studied in dose-expansion cohorts. The most frequent adverse events observed were periorbital edema (69%), anemia (55%), diarrhea (45%), thrombocytopenia (44%) and nausea (44%). Intracranial bleeding occurred in 13% overall, but in only 1% of patients without severe thrombocytopenia (platelets <50 × 10/l). In 53 response-evaluable patients, the overall response rate was 75%. The complete remission rate was 36%. Avapritinib elicited ≥50% reductions in marrow mast cells and serum tryptase in 92% and 99% of patients, respectively. Avapritinib induced deep and durable responses, including molecular remission of KIT D816V in patients with AdvSM, and was well tolerated at the recommended phase 2 dose of 200 mg daily.
Topics: Adult; Aged; Aged, 80 and over; Clinical Trials, Phase I as Topic; Dose-Response Relationship, Drug; Female; Humans; Male; Mastocytosis, Systemic; Middle Aged; Pyrazoles; Pyrroles; Triazines
PubMed: 34873347
DOI: 10.1038/s41591-021-01538-9 -
Molecular Diversity Oct 2022The chemistry of nitrogen-containing heterocyclic compound pyrrole and pyrrolidine has been a versatile field of study for a long time for its diverse biological and... (Review)
Review
The chemistry of nitrogen-containing heterocyclic compound pyrrole and pyrrolidine has been a versatile field of study for a long time for its diverse biological and medicinal importance. Biomolecules such as chlorophyll, hemoglobin, myoglobin, and cytochrome are naturally occurring metal complexes of pyrrole. These metal complexes play a vital role in a living system like photosynthesis, oxygen carrier, as well storage, and redox cycling reactions. Apart from this, many medicinal drugs are derived from either pyrrole, pyrrolidine, or by its fused analogs. This review mainly focuses on the therapeutic potential of pyrrole, pyrrolidine, and its fused analogs, more specifically anticancer, anti-inflammatory, antiviral, and antituberculosis. Further, this review summarizes more recent reports on the pyrrole, pyrrolidine analogs, and their biological potential.
Topics: Anti-Inflammatory Agents; Antiviral Agents; Chlorophyll; Coordination Complexes; Cytochromes; Heterocyclic Compounds; Myoglobin; Nitrogen; Oxygen; Pyrroles; Pyrrolidines
PubMed: 35079946
DOI: 10.1007/s11030-022-10387-8 -
Journal of Food and Drug Analysis Jul 2018Pyrrolizidine alkaloids (PAs) are phytotoxins identified in over 6000 plant species worldwide. Approximately 600 toxic PAs and PA N-oxides have been identified in about... (Review)
Review
Pyrrolizidine alkaloids (PAs) are phytotoxins identified in over 6000 plant species worldwide. Approximately 600 toxic PAs and PA N-oxides have been identified in about 3% flowering plants. PAs can cause toxicities in different organs particularly in the liver. The metabolic activation of PAs is catalyzed by hepatic cytochrome P450 and generates reactive pyrrolic metabolites that bind to cellular proteins to form pyrrole-protein adducts leading to PA-induced hepatotoxicity. The mechanisms that pyrrole-protein adducts induce toxicities have not been fully characterized. Methods for qualitative and quantitative detection of pyrrole-protein adducts have been developed and applied for the clinical diagnosis of PA exposure and PA-induced liver injury. This mini-review addresses the mechanisms of PA-induced hepatotoxicity mediated by pyrrole-protein adducts, the analytical methods for the detection of pyrrole-protein adducts, and the development of pyrrole-protein adducts as the mechanism-based biomarker of PA exposure and PA-induced hepatotoxicity.
Topics: Animals; Biomarkers; Chemical and Drug Induced Liver Injury; Humans; Liver; Proteins; Pyrroles; Pyrrolizidine Alkaloids
PubMed: 29976414
DOI: 10.1016/j.jfda.2018.05.005 -
Molecules (Basel, Switzerland) Jan 2016Pyrrolo[1,4]benzodiazepines are tricyclic compounds that are considered "privileged structures" since they possess a wide range of biological activities. The first... (Review)
Review
Pyrrolo[1,4]benzodiazepines are tricyclic compounds that are considered "privileged structures" since they possess a wide range of biological activities. The first encounter with these molecules was the isolation of anthramycin from cultures of Streptomyces, followed by determination of the X-ray crystal structure of the molecule and a study of its interaction with DNA. This opened up an intensive synthetic and biological study of the pyrrolo[2,1-c][1,4]benzodiazepines that has culminated in the development of the dimer SJG-136, at present in Phase II clinical trials. The synthetic efforts have brought to light some new synthetic methodology, while the contemporary work is focused on building trimeric pyrrolo[2,1-c][1,4]benzodiazepines linked together by various heterocyclic and aliphatic chains. It is the broad spectrum of biological activities of pyrrolo[1,2-a][1,4]benzodiazepines that has maintained the interest of researchers to date whereas several derivatives of the even less studied pyrrolo[1,2-d][1,4]benzodiazepines were found to be potent non-nucleoside HIV-1 reverse transcriptase inhibitors. The present review is an update on the synthesis of pyrrolo[2,1-c][1,4]benzodiazepines since the last major review of 2011, while the overview of the synthesis of the other two tricyclic isomers is comprehensive.
Topics: Anti-HIV Agents; Antineoplastic Agents; Benzodiazepines; Clinical Trials as Topic; Cyclization; DNA; HIV Infections; Humans; Molecular Structure; Neoplasms; Pyrroles; Structure-Activity Relationship
PubMed: 26828475
DOI: 10.3390/molecules21020154