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The presence of NSAIDs may affect the binding capacity of serum albumin to the natural products hymecromone and umbelliferone.
Int J Biol Macromol
December 2024
Departament of Organic Chemistry, Institute of Chemistry, Federal Rural University of Rio de Janeiro (UFRRJ), Seropédica 23890-000, RJ, Brazil. Electronic address:
The natural products 7-hydroxycoumarin (7HC) and 7-hydroxy-4-methylcoumarin (7H4MC), known as umbelliferone and hymecromone, respectively, are one of the simplest structural examples from coumarin's family, showing several biological activities. Bovine serum albumin (BSA) is the main model protein used in laboratory experiments to characterize the biophysical capacity of potential drugs to be carried until the target in the bloodstream. Thus, the interaction BSA:7HC and BSA:7H4MC was biophysically characterized by circular dichroism (CD), steady-state, and time-resolved fluorescence techniques combined with molecular docking calculations via cross-docking approach to better correlate with the biological medium.
View Article and Find Full Text PDFHymecromone Promotes Longevity and Insulin Sensitivity in Mice.
Cells
October 2024
Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University, Stanford, CA 94305, USA.
Given that the extracellular matrix polymer hyaluronan (HA) has been implicated in longevity, we asked whether 4-methylumbelliferone (4-MU), an inhibitor of HA synthesis, impacts lifespan in mice. We designed a prospective study of long-term administration of 4-MU with conventional C57BL/6J mice. We find that 4-MU extends median survival from 122 weeks (control) to 154 weeks (4-MU), an increase of 32 weeks ( < 0.
View Article and Find Full Text PDF6-O-alkyl 4-methylumbelliferyl-β-D-glucosides as selective substrates for GBA1 in the discovery of glycosylated sterols.
J Lipid Res
November 2024
Medical Biochemistry, Leiden Institute of Chemistry (LIC), Leiden University, RA Leiden, The Netherlands. Electronic address:
Article Synopsis
- Gaucher disease (GD) is a genetic lysosomal storage disorder caused by a deficiency in the enzyme glucocerebrosidase (GBA1), and its diagnosis typically employs assays that can be compromised by background activity from other enzymes.
- Researchers have developed a selective fluorogenic substrate called 6-O-alkyl-4MU-β-Glc, which effectively targets GBA1 and avoids interference from other enzymes, making it suitable for diagnosing GD.
- Additionally, analyses of spleen samples from GD patients revealed increased levels of acylated and regular glycosyl lipids, highlighting a potential link between plant-derived glycosyl phytosterols and the disease, raising questions about their role in developing conditions like Parkinson's
Targeting hyaluronan metabolism-related molecules associated with resistant tumor-initiating cells potentiates chemotherapy efficacy in lung cancer.
Sci Rep
July 2024
Cancer Immunobiology Laboratory, Instituto de Investigaciones en Medicina Traslacional, Universidad Austral-Consejo Nacional de Investigaciones Científicas y Técnicas, Pilar, Argentina.
The success of chemotherapy regimens in patients with non-small cell lung cancer (NSCLC) could be restricted at least in part by cancer stem cells (CSC) niches within the tumor microenvironment (TME). CSC express CD133, CD44, CD47, and SOX2, among other markers and factors. Analysis of public data revealed that high expression of hyaluronan (HA), the main glycosaminoglycan of TME, correlated positively with CSC phenotype and decreased disease-free interval in NSCLC patients.
View Article and Find Full Text PDFGlycooligomer-Functionalized Catalytic Nanocompartments Co-Loaded with Enzymes Support Parallel Reactions and Promote Cell Internalization.
Biomacromolecules
July 2024
Department of Chemistry, University of Basel, Mattenstrasse 22, Basel 4002, Switzerland.
A major shortcoming associated with the application of enzymes in drug synergism originates from the lack of site-specific, multifunctional nanomedicine. This study introduces catalytic nanocompartments (CNCs) made of a mixture of PDMS--PMOXA diblock copolymers, decorated with glycooligomer tethers comprising eight mannose-containing repeating units and coencapsulating two enzymes, providing multifunctionality by their in situ parallel reactions. Beta-glucuronidase (GUS) serves for local reactivation of the drug hymecromone, while glucose oxidase (GOx) induces cell starvation through glucose depletion and generation of the cytotoxic HO.
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