Aryloxy phosphoroamidate triesters, known as ProTides, are a class of prodrugs developed to enhance the physicochemical and pharmacological properties of therapeutic nucleosides. This approach has been extensively investigated in the antiviral and anticancer areas leading to three prodrugs on the market and several others in clinical stage. In this article we have prepared the PS analogues of three ProTides that have reached the clinic as anticancer agents. These novel PS ProTides were tested for their capacity in enzymatic activation and for their cytotoxic properties against a panel of solid and liquid tumor cell lines. As expected, the replacement of the PO with a PS bond led to increased metabolic stability albeit concomitant to a decrease in potency. Surprisingly, the intermediate formed after the first activation step of a thiophosphoramidate with carboxypeptidase Y is not the expected PS aminoacyl product but the corresponding PO aminoacyl compound.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmc.2024.117696 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Enzymatic asymmetric synthesis of l-phenylglycine by amino acid dehydrogenases has potential for industrial applications; however, this is hindered by their low catalytic efficiency toward high-concentration substrates. We identified and characterized a novel leucine dehydrogenase (LeuDH) with a high catalytic efficiency for benzoylformic acid via directed metagenomic approaches. Further, we obtained a triple-point mutant LeuDH-EER (D332E/G333E/L334R) with improved stability and catalytic efficiency through the rational design of distal loop 13.
View Article and Find Full Text PDFMolecular Mechanism Behind the Capture of Fluorinated Gases by Metal-Organic Frameworks.
Nanomicro Lett
January 2025
College of Environmental Science and Engineering, State Key Laboratory of Pollution Control and Resource Reuse, Tongji University, Siping Rd 1239, Shanghai, 200092, People's Republic of China.
Fluorinated gases (F-gases) play a vital role in the chemical industry and in the fields of air conditioning, refrigeration, health care, and organic synthesis. However, the direct emission of waste gases containing F-gases into the atmosphere contributes to greenhouse effects and generates toxic substances. Developing porous materials for the energy-efficient capture, separation, and recovery of F-gases is highly desired.
View Article and Find Full Text PDFRole of major cardiovascular surgery-induced metabolic reprogramming in acute kidney injury in critical care.
Intensive Care Med
January 2025
Center for Disease Mechanisms Research, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal.
Purpose: Major cardiovascular surgery imposes high physiologic stress, often causing severe organ dysfunction and poor outcomes. The underlying mechanisms remain unclear. This study investigated metabolic changes induced by major cardiovascular surgery and the potential role of identified metabolic signatures in postoperative acute kidney injury (AKI).
View Article and Find Full Text PDFUnveiling astaxanthin: biotechnological advances, delivery systems and versatile applications in nutraceuticals and cosmetics.
Arch Microbiol
January 2025
School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, 632014, India.
Astaxanthin (ASX), "king of carotenoids", is a xanthophyll carotenoid that is characterized by a distinct reddish-orange hue, procured from diverse sources including plants, microalgae, fungi, yeast, and lichens. It exhibits potent antioxidant and anti-ageing properties and has been demonstrated to mitigate ultraviolet-induced cellular and DNA damage, enhance immune system function, and improve cardiovascular diseases. Despite its broad utilization across nutraceutical, cosmetic, aquaculture, and pharmaceutical sectors, the large-scale production and application of ASX are constrained by the limited availability of natural sources, low production yields and stringent production requirements.
View Article and Find Full Text PDFSuper-Resolved Mapping of Electrochemical Reactivity in Single 3D Catalysts.
Nano Lett
January 2025
Institute of Nanochemistry and Nanobiology, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, P.R. China.
Crystals with three-dimensional (3D) stereoscopic structures, characterized by diverse shapes, crystallographic planes, and morphologies, represent a significant advancement in catalysis. Differentiating and quantifying the catalytic activity of specific surface facets and sites at the single-particle level is essential for understanding and predicting catalytic performance. This study employs super-resolution radial fluctuations electrogenerated chemiluminescence microscopy (SRRF-ECLM) to achieve high-resolution mapping of electrocatalytic activity on individual 3D CuO crystals, including cubic, octahedral, and truncated octahedral structures.
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!