Three half-ester derivatives 10-12 of 5'-O-2',3'-dideoxydidanosine (DDI, 1) have been synthesized. The compounds exhibited excellent correlation between partition coefficients LogP and relative in vitro bovine serum albumin binding. Using high-performance liquid chromatography-mass spectrometry (LC-MS), DDI (1) was quantitatively determined in rat plasma after intravenous injection of the azelaic acid monoester derivative (11) of DDI. The pharmacokinetic data obtained for DDI were consistent with literature. The pharmacokinetic profile of 11 showed no significant difference in AUC(0-360) or curve shape compared to the parent drug DDI (1). The data indicate that the prodrug was converted to DDI within minutes after administration. High relative protein binding in vitro holds a promise for validity of the concept using more stable linker bonds.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ejmech.2009.04.008 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
rs762855 single nucleotide polymorphism modulates the risk for diffuse-type gastric cancer in females: a genome-wide association study in the Korean population.
Gastric Cancer
January 2025
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-Do, South Korea.
Background: Intestinal-type gastric cancer (IGC) and diffuse-type gastric cancer (DGC) exhibit different prevalence rates between sexes. While environmental factors like Helicobacter pylori infection and alcohol consumption contribute to these differences, they do not fully account for them, suggesting a role for host genetic factors.
Methods: We conducted a meta-analysis to explore associations between single nucleotide polymorphisms (SNPs) and the risk of IGC or DGC.
Green Tea Polyphenol Epigallocatechin Gallate Interactions with Copper-Serum Albumin.
Molecules
January 2025
Department of Chemistry & Biochemistry, Miami University, Oxford, OH 45056, USA.
Epigallocatechin gallate (EGCg), an abundant phytochemical in green tea, is an antioxidant that also binds proteins and complex metals. After gastrointestinal absorption, EGCg binds to serum albumin in the hydrophobic pocket between domains IIA and IIIA and overlaps with the Sudlow I site. Serum albumin also has two metal binding sites, a high-affinity N-terminal site (NTS) site that selectively binds Cu(II), and a low-affinity, less selective multi-metal binding site (MBS).
View Article and Find Full Text PDFCo-Existing Nanoplastics Further Exacerbates the Effects of Triclosan on the Physiological Functions of Human Serum Albumin.
Life (Basel)
January 2025
School of Environment and Geography, Qingdao University, Qingdao 266071, China.
The potential health risks posed by the coexistence of nanoplastics (NPs) and triclosan (TCS) have garnered significant attention. However, the effects and underlying mechanisms of NPs and TCS on key functional proteins at the molecular level remain poorly understood. This study reports the effect of polystyrene nanoplastics (PSNPs) on the binding of TCS to human serum albumin (HSA) using multispectral methods and molecular simulation systems.
View Article and Find Full Text PDFImplications of Mineralization Biomarkers in Breast Cancer Outcomes Beyond Calcifications.
Int J Mol Sci
January 2025
Department of Experimental Medicine, TOR, University of Rome "Tor Vergata", 00133 Rome, Italy.
The aim of this work was to explore the biomarkers associated with epithelial to mesenchymal transition (EMT) and mineralization processes as new prognostic factors across different breast cancer phenotypes. To this end, 133 breast biopsies, including benign and malignant lesions, with or without microcalcifications, were retrospectively collected. Immunohistochemical analysis was performed to evaluate the expression of vimentin, BMP-2, BMP-4, RANKL, Runx2, OPN, PTX3, and SDF-1, while Kaplan-Meier plots were used to assess their prognostic impact on overall survival in a dataset of 2976 breast cancer patients.
View Article and Find Full Text PDFMetallothionein-1A (MT1A) Gene Variability May Play a Role in Female Frailty: A Preliminary Study.
Genes (Basel)
December 2024
Department of Biology, Ecology and Earth Sciences, University of Calabria, 87036 Rende, CS, Italy.
Background/objectives: Frailty is a complex geriatric syndrome resulting in decreased physiological reserve. While genetics plays a role, the underlying mechanisms remain unsolved. Metallothioneins (MTs), metal-binding proteins with high affinity for zinc, an essential mineral for many physiological functions, are involved in processes including oxidative stress and inflammation.
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!