AI Article Synopsis
- Synthesized novel azetidin-2-ones (compounds 5-8) through [2 + 2] cycloaddition of imines and ketenes to evaluate their cholesterol-lowering effects in hypercholesterolemia caused by diet and diabetes.
- Compounds 5a and 7a significantly reduced serum cholesterol levels in both acute and chronic dietary models, and compound 5a notably increased HDL-cholesterol levels.
- In diabetes-induced hypercholesterolemia models, test compounds effectively lowered total cholesterol, with a greater reduction observed in the initial prevention phase compared to the later phase, while discussing the structure-activity relationship (SAR) and proposing a mechanism of action.
Article Abstract
Some novel substituted azetidin-2-ones (5-8) were synthesized via [2 + 2] cycloaddition reactions of imines and ketenes and evaluated for their ability to prevent diet and diabetes induced hypercholesterolemia. The test compounds 5a and 7a significantly (p < 0.01) inhibited the rise in serum total cholesterol induced by peanut oil (5.5%), cholesterol (1.5%) and cholic acid (0.5%) diet in both acute and chronic models in a dose dependent manner. Compound 5a also raised the high density lipoprotein-cholesterol levels in chronic diet models by peanut oil (5.5%), cholesterol (1.5%) and cholic acid (0.5%). In a diabetes induced model of hypercholesterolemia, the test compounds were evaluated for preventing diabetes-induced hypercholesterolemia (protocol 1) as well as for lowering post diabetic hypercholesterolemia (protocol 2). Test compounds 5a-g and 7a-d significantly (p < 0.05) reduced serum total cholesterol with a greater reduction in protocol 1 as compared with protocol 2. Based on SAR studies, the substituents that favor hypocholesterolemic activity around the azetidin-2-one nucleus are discussed and a possible mechanism of action is proposed on the basis of their differential effects in two protocols of diabetes-induced hypercholesterolemia.
Download full-text PDF |
Source |
|---|
Publication Analysis
Top Keywords
Similar Publications
Alcohol-induced gut microbial reorganization and associated overproduction of phenylacetylglutamine promotes cardiovascular disease.
Nat Commun
December 2024
Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
The mechanism(s) underlying gut microbial metabolite (GMM) contribution towards alcohol-mediated cardiovascular disease (CVD) is unknown. Herein we observe elevation in circulating phenylacetylglutamine (PAGln), a known CVD-associated GMM, in individuals living with alcohol use disorder. In a male murine binge-on-chronic alcohol model, we confirm gut microbial reorganization, elevation in PAGln levels, and the presence of cardiovascular pathophysiology.
View Article and Find Full Text PDFA truncated isoform of Connexin43 caps actin to organize forward delivery of full-length Connexin43.
J Cell Biol
March 2025
Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT, USA.
While membrane proteins such as ion channels continuously turn over and require replacement, the mechanisms of specificity of efficient channel delivery to appropriate membrane subdomains remain poorly understood. GJA1-20k is a truncated Connexin43 (Cx43) isoform arising from translation initiating at an internal start codon within the same parent GJA1 mRNA and is requisite for full-length Cx43 trafficking to cell borders. GJA1-20k does not have a full transmembrane domain, and it is not known how GJA1-20k enables forward delivery of Cx43 hemichannels.
View Article and Find Full Text PDFMulti-Functional Bio-HJzyme Engineered Polyetheretherketone Implant with Cascade-Amplification Therapeutic Capabilities Toward Intractable Implant-Associated Infections.
Small
December 2024
State Key Laboratory of Oral Diseases, School of Chemical Engineering, National Center for Stomatology & National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, 610041, China.
Intractable implant-associated infections (IAIs) are the primary cause of prosthetic implant failure, particularly in the context of diabetes mellitus. There is an urgent need to design and construct versatile engineered implants integrated with cascade amplification therapeutic modality to significantly improve the treatment of diabetic IAIs. To address this issue, a multi-functional MXene/AgPO@glucose oxidase bio-heterojunction enzyme (M/A@GOx bio-HJzyme) coating is developed, which is decorated with an inert sulfonated polyetheretherketone implant (SP-M/A@G) via hydrothermal treatment and layered deposition.
View Article and Find Full Text PDFBroccoli () leaves exhibit significant antidiabetic potential in alloxan-induced diabetic rats: the putative role of ABC vacuolar transporter for accumulation of Quercetin and Kaempferol.
Front Pharmacol
December 2024
Department of Biochemistry, Quaid-i-Azam University, Islamabad, Pakistan.
Background: The global prevalence of diabetes among adults over 18 years of age is expected to increase from 10.5% to 12.2% (between 2021 and 2045).
View Article and Find Full Text PDFEffect of leaf extract and its active components on heart muscle cell apoptosis induced by hyperglycemia.
Open Vet J
November 2024
Department of Anatomical Pathology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.
Background: Hyperglycemia is a condition in which blood sugar levels increase excessively due to a variety of factors, one of which is the body's inability to regulate insulin properly. Diabetes closely relates to this condition, which significantly contributes to premature death and disability. Long-term diabetes treatment accompanied by a strict diet provides real results in controlling blood glucose levels but can cause side effects.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!