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Journal of Medicinal Chemistry Sep 1980Series of 5-phenoxy-2(1H)-pyrimidinones, 5-phenoxy-4(3H)-pyrimidinones, and related compounds were prepared in a follow-up of a lead prepared as a potential cyclic...
Series of 5-phenoxy-2(1H)-pyrimidinones, 5-phenoxy-4(3H)-pyrimidinones, and related compounds were prepared in a follow-up of a lead prepared as a potential cyclic nucleotide regulating agent. Compounds were evaluated for bronchodilator activity in histamine-challenged guinea pigs and for anticulcer activity in a cold-restraint, stressed rat ulcer model. Bronchodilator activity comparable to, or greater than, that of theophylline was found in both the 2(1H)- and 4(3H)-pyrimidinone series and was most prominent in analogues containing either an electron-withdrawing or -donating substituent in the para position of the phenoxy ring. Significant antiulcer activity was observed only in the 2(1H)-pyrimidinone series among three closely related analogues. One of these, 5-(m-methylphenoxy)-2(1H)-pyrimidinone (3), exhibited more potent antiulcer effects than the clinically useful antiulcer agent carbenoxolone, without demonstrating bronchodilator activity.
Topics: Animals; Anti-Ulcer Agents; Bronchodilator Agents; Female; Gastric Mucosa; Guinea Pigs; Mucus; Pyrimidinones; Rats; Structure-Activity Relationship
PubMed: 7411545
DOI: 10.1021/jm00183a012 -
Current Pharmaceutical Design 2018Cancer cachexia, one of the metabolic syndromes caused by cancer, is a devastating and miserable condition encountered in more than 50% of terminal cancer patients... (Review)
Review
Cancer cachexia, one of the metabolic syndromes caused by cancer, is a devastating and miserable condition encountered in more than 50% of terminal cancer patients presenting with significant weight loss associated with skeletal muscle atrophy and fat loss. Though cachexia may account for up to 20% of cancer deaths, no significant treatment is still lacking and is of urgent unmet medical need in cancer treatment. Therefore, understanding the underlying molecular mechanisms is essential for anticipating therapeutic approaches. Since the primary events driving cachexia are mediated via either the central nervous system relatedor inflammation related-anorexia, hypoanabolism, and hypercatabolism, therapy usually targets nutritional support to compensate reduced food intake along with some anti-inflammatory agents to cover specific inflammation-related metabolic derangement, and encourages exercise to supplement reduced physical activity, but all proven to be not so effective so far. Therefore, combination therapies such as a standard multi-modal package including an anorexic agent, megestrol acetate, and anti-inflammatory agent coupled with the development of potential novel therapeutics promise a new era in rescuing patients from cancer cachexia. In this review, we propose the potential application of BPC157, one of the active cytoprotective agents isolated from gastric juices for cancer cachexia. Before clinical trial, we introduced the evidence showing BPC157 rescued from cancer cachexia supported with explored mode of actions.
Topics: Animals; Anti-Ulcer Agents; Cachexia; Gastric Juice; Humans; Neoplasms; Peptide Fragments; Proteins
PubMed: 29898649
DOI: 10.2174/1381612824666180614082950 -
DICP : the Annals of Pharmacotherapy Oct 1989The use of medications for the treatment of gastrointestinal ulcers has evolved to a great extent since the early days of therapy with diet and antacids. Today a number... (Review)
Review
The use of medications for the treatment of gastrointestinal ulcers has evolved to a great extent since the early days of therapy with diet and antacids. Today a number of different agents are available to treat the causative factors of ulcer formation. Currently, antacids, histamine2-receptor antagonists, and sucralfate are considered frontline therapies suitable for most patients. The future also looks promising for newer agents, such as omeprazole and prostaglandin analogs. The purpose of this article is to provide practitioners with an understanding of the achieved more efficiently and effectively.
Topics: Anti-Ulcer Agents; Humans; Peptic Ulcer; Stomach Ulcer
PubMed: 2683421
DOI: 10.1177/1060028089023s1002 -
Nihon Yakurigaku Zasshi. Folia... Sep 1995Gastrin plays an important role in gastrointestinal functions such as gastric secretion and mucosal growth. The hypergastrinemia that results from long-term treatment... (Review)
Review
Gastrin plays an important role in gastrointestinal functions such as gastric secretion and mucosal growth. The hypergastrinemia that results from long-term treatment with proton pump inhibitors and histamine H2-receptor antagonists induces hyperplasia of enterochromaffin-like (ECL) cells and increases the secretory response to pentagastrin (acid rebound). Recently, potent and selective gastrin/CCK-B-receptor antagonists, L-365,260, PD136450 and YM022, have been developed. These compounds inhibit basal and meal-stimulated acid secretion as well as pentagastrin-stimulated acid secretion in rats and dogs. Long-term treatment with gastrin/CCK-B-receptor antagonists does not cause hyperplasia of ECL cells and acid rebound at all. Moreover, they prevent hyperplasia and acid rebound induced by proton pump inhibitors and histamine H2-receptor antagonists. Therefore, gastrin/CCK-B-receptor antagonists are suggested to be novel antiulcer and antisecretory agents without potential for acid rebound, hyperplasia and carcinoid.
Topics: Animals; Anti-Ulcer Agents; Depression, Chemical; Dogs; Gastric Acid; Gastric Mucosa; Hyperplasia; Rats; Receptor, Cholecystokinin B; Receptors, Cholecystokinin
PubMed: 8529962
DOI: 10.1254/fpj.106.171 -
Antimicrobial Agents and Chemotherapy Aug 2002The benzimidazole compound omeprazole, used widely for the treatment of peptic ulcer disease, inhibits the growth of Leishmania donovani, the causative agent of visceral...
The benzimidazole compound omeprazole, used widely for the treatment of peptic ulcer disease, inhibits the growth of Leishmania donovani, the causative agent of visceral leishmaniasis. Promastigotes cultured at acidic pH and amastigotes within infected macrophages are reduced 90% or more with 150 microM omeprazole. Antiparasitic action of the drug is due to its inhibition of the P-type K(+),H(+)-ATPase on the surface membrane. This enzyme is important for pH homeostasis and the maintenance of proton motive force across the membrane in Leishmania. The drug is effective only at acidic pH, a condition that mimics the in vivo environment within the phagolysosomal vesicles where the amastigote form of the parasite resides. Omeprazole deserves consideration as an alternative to currently available chemotherapeutics, which have severe toxic side effects.
Topics: Animals; Anti-Ulcer Agents; Antiprotozoal Agents; Cell Membrane; Dose-Response Relationship, Drug; H(+)-K(+)-Exchanging ATPase; Hydrogen; Hydrogen-Ion Concentration; Leishmania donovani; Macrophages, Peritoneal; Mice; Mice, Inbred CBA; Omeprazole; Proton Pump Inhibitors
PubMed: 12121934
DOI: 10.1128/AAC.46.8.2569-2574.2002 -
Journal of Postgraduate Medicine 2002
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Benzimidazoles; Clinical Trials as Topic; Humans; Omeprazole; Peptic Ulcer; Rabeprazole
PubMed: 12082341
DOI: No ID Found -
Mini Reviews in Medicinal Chemistry 2019Here in we report the number of strategies for the synthesis of differently substituted benzimidazole derivatives. The protocols involved in the syntheses of these... (Review)
Review
Here in we report the number of strategies for the synthesis of differently substituted benzimidazole derivatives. The protocols involved in the syntheses of these derivatives were one-pot or multi-component. The characterization studies of these derivatives were carried by using different spectroscopic techniques (1H NMR, 13C NMR and MS) and elemental analyses. The biological screening studies revealed that these benzimidazole derivatives show potential antibacterial as well as antifungal behavior. These benzimidazole derivatives not only depicted potential antiulcer properties but also showed moderate to good anticancer/cytotoxic behavior against different cancer cell lines.
Topics: Anti-Infective Agents; Anti-Ulcer Agents; Benzimidazoles; Infections; Ulcer
PubMed: 30332950
DOI: 10.2174/1381612824666181017102930 -
Anaerobe Jun 2022To evaluate baseline risk for hospital onset Clostridioides difficile infection (HO-CDI) and the association with the use of antiulcer agents among patients undergoing...
Association between antiulcer agents and Clostridioides difficile infection in patients receiving antibiotics: A retrospective cohort study using the diagnosis procedure combination database in Japan.
OBJECTIVES
To evaluate baseline risk for hospital onset Clostridioides difficile infection (HO-CDI) and the association with the use of antiulcer agents among patients undergoing antibiotic therapy in Japan.
METHODS
We conducted a retrospective cohort study using Japanese Diagnosis Procedure Combination database. Between July 2018 and January 2019, patients aged ≥18 years were included if they started antibiotics within two days of hospital admission. We defined exposure as proton pump inhibitors or histamine 2 receptor antagonists starting from day 2 to day 4 and the primary outcome as HO-CDI within 30 days. We performed multivariable analyses with complete cases using the propensity score (inverse probability treatment weighting [IPTW]) and several sensitivity analyses.
RESULTS
In total, 87,137 patients were included. The median age was 78 years; 52.0% were men, and 23.6% received antiulcer agents. Within 30 days of admission, HO-CDI were observed in 0.41% and 0.26% of the antiulcer agent and control groups, respectively. IPTW revealed a positive association between antiulcer agents and HO-CDI (adjusted odds ratio, 1.33; 95% confidence interval [CI]: 1.13, 1.56). In the IPTW method, the risk difference was smaller (0.09%, 95% CI: 0.04%, 0.15%).
CONCLUSION
The use of antiulcer agents in patients with antibiotics was associated with HO-CDI in Japan. However, the baseline risk and the difference in HO-CDI event rates were small; thus, as per several clinical practice guidelines, it is important to monitor antiulcer agent use and discontinue unnecessary use. The baseline risk should be considered when clinically evaluating the association between antiulcer agents and HO-CDI.
Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Anti-Ulcer Agents; Clostridioides difficile; Clostridium Infections; Cross Infection; Female; Humans; Japan; Male; Retrospective Studies
PubMed: 35202792
DOI: 10.1016/j.anaerobe.2022.102537 -
Chemico-biological Interactions Apr 2020Lupeol (1) was isolated from hexane branch extract of Maytenus salicifolia and the Lupeol stearate (2), Lupeol palmitate (3), Lupeol myristate (4), Lupeol laurate (5)...
Lupeol (1) was isolated from hexane branch extract of Maytenus salicifolia and the Lupeol stearate (2), Lupeol palmitate (3), Lupeol myristate (4), Lupeol laurate (5) and Lupeol caprylate (6) were obtained reacting 1 with an adequate carboxylic acid. Swiss mice were treated with vehicle, carbenoxolone or Lupeol esters before administration of ethanol/HCl or indomethacin. Additionally, the involvement of nitric oxide (NO), sulfhydryl compounds (NP-SH), α-2 adrenergic receptors (α2-AR) and prostaglandins (PGE) in antiulcer effects was investigated using appropriate inhibitors or antagonist. Oxidative and inflammatory parameters were measured after euthanasia and anti-secretory effects was evaluated in pylorus-ligated rats. Ethanol/HCl ulcerated the gastric mucosa by 64.45 ± 6.58 mm, which the oral treatment with 1, 4 and 6 (10 mg/kg), and 3 and 5 (30 mg/kg) reduced the lesion area. Interestingly, 2 reduced the gastric ulcer by oral route in a potent and dose-dependent manner (ED = 0.40 mg/kg), which was accompanied by the increase in reduced glutathione levels and by the reduction of lipids peroxidation and myeloperoxidase and superoxide dismutase activities. Moreover, 2 (0.1 mg/kg) also prevented the ulcerogenesis by intraperitoneal route. The participation of NO, NP-SH, α2-AR and PGE in 2-mediated gastroprotection was confirmed. In indomethacin-induced ulcer, 2 (1 mg/kg, p.o) also reduced the ulcer area and increased the PGE levels. However, 2 did not alter the gastric acid secretion. Therefore, these findings indicate that the obtention of 2 potentiated the antiulcer activity of 1 and that this compound can elicit gastroprotective action due a diversified mode of action.
Topics: Animals; Anti-Ulcer Agents; Disease Models, Animal; Esterification; Ethanol; Gastric Mucosa; Hydrochloric Acid; Indomethacin; Mice; NG-Nitroarginine Methyl Ester; Nitric Oxide; Pentacyclic Triterpenes; Rats; Rats, Wistar; Stomach Ulcer; Structure-Activity Relationship
PubMed: 32006539
DOI: 10.1016/j.cbi.2020.108964 -
Journal of Ethnopharmacology May 2012Rhizome of Zingiber montanum has been extensively used as a folk medicine to ameliorate peptic ulcer at northern part of Bangladesh.
ETHNOPHARMACOLOGICAL RELEVANCE
Rhizome of Zingiber montanum has been extensively used as a folk medicine to ameliorate peptic ulcer at northern part of Bangladesh.
AIM OF THE STUDY
To identify the antiulcer principle of the MeOH extract of the rhizome of Zingiber montanum by an ex vivo bioassay guided chromatographic separation and purification, and structure elucidation of the purified compound by spectroscopic methods.
MATERIALS AND METHODS
Dried powder of Zingiber montanum rhizomes was extracted with MeOH. The antiulcer activity of the crude extract and its chromatographic fractions were evaluated by the inhibition of 1N HCl induced gastric lesions in Swiss albino mice. The pure compound was purified from the active fraction by crystallization with hexanes. Structure of the pure compound was elucidated by spectroscopic methods. The antiulcer activity of the pure compound was evaluated by the inhibition of 1N HCl, 95% ethanol and indomethacin induced gastric lesions in mice.
RESULTS
The MeOH extract of Zingiber montanum showed 61.97% and 83.10% inhibition of the 1N HCl induced gastric lesions at doses of 200mg/kg and 400mg/kg, respectively, in mice. Chromatographic separation on silica gel of the extract was yielded seven fractions and the fraction 2 was found to have most potent antiulcer activity in mice. This fraction showed 77.46% inhibition of the 1N HCl induced gastric lesions at a dose of 40mg/kg in mice. Crystallization of the fraction yielded 1 (zerumbone, 180mg). It showed statistically 45.77% and 92.25% inhibition of 1N HCl induced gastric lesions in mice at doses of 20mg/kg and 40mg/kg, respectively. It also showed 29.07% and 45.35% inhibition of 95% ethanol induced gastric mucosal damage, and 64.76% and 72.38% inhibition of indomethacin induced gastric lesions in mice at doses of 20mg/kg and 40mg/kg, respectively.
CONCLUSION
Zerumbone (1) showed potent cytoprotective effect against necrotizing agent (HCl) and non-steroidal anti-inflammatory drug (indomethacin) induced gastric ulceration. It also exhibited moderate cytoprotective effect against noxious agent (EtOH) induced gastric lesions. It can be considered as a promising new antiulcer natural drug lead.
Topics: Animals; Anti-Ulcer Agents; Chromatography; Cytoprotection; Disease Models, Animal; Dose-Response Relationship, Drug; Ethanol; Female; Gastric Mucosa; Hydrochloric Acid; Indomethacin; Magnetic Resonance Spectroscopy; Male; Methanol; Mice; Molecular Structure; Phytotherapy; Plants, Medicinal; Rhizome; Sesquiterpenes; Solvents; Stomach Ulcer; Zingiberaceae
PubMed: 22366683
DOI: 10.1016/j.jep.2012.01.046