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1.
World J Gastrointest Pharmacol Ther ; 15(3): 92305, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38846968

ABSTRACT

BACKGROUND: Peptic ulcer disease (PUD) remains a significant healthcare burden, contributing to morbidity and mortality worldwide. Despite advancements in therapies, its prevalence persists, particularly in regions with widespread nonsteroidal anti-inflammatory drugs (NSAIDs) use and Helicobacter pylori infection. AIM: To comprehensively analyse the risk factors and outcomes of PUD-related upper gastrointestinal (GI) bleeding in Pakistani population. METHODS: This retrospective cohort study included 142 patients with peptic ulcer bleeding who underwent upper GI endoscopy from January to December 2022. Data on demographics, symptoms, length of stay, mortality, re-bleed, and Forrest classification was collected. RESULTS: The mean age of patients was 53 years, and the majority was men (68.3%). Hematemesis (82.4%) and epigastric pain (75.4%) were the most common presenting symptoms. Most patients (73.2%) were discharged within five days. The mortality rates at one week and one month were 10.6% and 14.8%, respectively. Re-bleed within 24 h and seven days occurred in 14.1% and 18.3% of patients, respectively. Most ulcers were Forrest class (FC) III (72.5%). Antiplatelet use was associated with higher mortality at 7 and 30 d, while alternative medications were linked to higher 24-hour re-bleed rates. NSAID use was associated with more FC III ulcers. Re-bleed at 24 h and 7 d was strongly associated with one-week or one-month mortality. CONCLUSION: Antiplatelet use and rebleeding increase the risk of early mortality in PUD-related upper GI bleeding, while alternative medicines are associated with early rebleeding.

3.
Bioorg Chem ; 83: 29-46, 2019 03.
Article in English | MEDLINE | ID: mdl-30339862

ABSTRACT

Current study is based on the biology-oriented drug synthesis (BIODS) of S-naproxen (NSAID) derivatives and the evaluation of their urease inhibitory potential. In this regard, a variety of S-naproxen derivatives 2-39 including hydrazide 1, Schiff bases 2-21, aroyl substituted hydrazides 22-24, sulfohydrazides 25-34, 2-mercapto oxadiazole 35, phenacyl substituted 2-mercapto oxadiazoles 36-39 were synthesized under the umbrella of BIODS by simple chemical transformation of its pharmacophoric carboxylic group. Compounds 1-39 were evaluated for in vitro urease inhibitory activity and most of them showed good to moderate inhibitory potential in the range of IC50 = 14.01 ±â€¯0.23-76.43 ±â€¯0.8 µM as compared to standard acetohydroxamic acid (IC50 = 27.0 ±â€¯0.5 µM). Limited structure-activity relationship (SAR) was established in order to rationalize the participation of varying groups (R) in the inhibitory potential of compounds. Molecular docking study on all active compounds was also carried out to decipher the interactions detail of the ligand with the receptors of active site of enzyme.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Enzyme Inhibitors/pharmacology , Naproxen/pharmacology , Urease/antagonists & inhibitors , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Humans , Molecular Docking Simulation , Molecular Structure , Naproxen/chemical synthesis , Naproxen/chemistry , Structure-Activity Relationship , Urease/metabolism
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