Medicinal Chemistry of Drugs with N-Oxide Functionalities

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(7), P. 5168 - 5184

Published: March 29, 2024

Molecules with N-oxide functionalities are omnipresent in nature and play an important role Medicinal Chemistry. They synthetic or biosynthetic intermediates, prodrugs, drugs, polymers for applications drug development surface engineering. Typically, the group is critical biomedical of these molecules. It may provide water solubility decrease membrane permeability immunogenicity. In other cases, has a special redox reactivity which targeting and/or cytotoxicity. Many underlying mechanisms have only recently been discovered, number N-oxides healthcare field rapidly growing. This Perspective article gives short summary properties their synthesis. also provides discussion current explains basic molecular responsible biological activity.

Language: Английский

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Decoration of 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA) with N‐oxides increases the T₁ relaxivity of Gd‐complexes

ChemistryOpen, Journal Year: 2024, Volume and Issue: 13(7)

Published: Jan. 15, 2024

Abstract High complex stability and longitudinal relaxivity of Gd‐based contrast agents are important requirements for magnetic resonance imaging (MRI) because they ensure patient safety contribute to measurement sensitivity. Charged zwitterionic Gd 3+ ‐complexes the well‐known chelator 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA) provide an excellent basis development safe sensitive agents. In this report, we describe synthesis DOTA‐NOx, a DOTA derivative with four N ‐oxide functionalities via “click” functionalization tetraazide DOTAZA. The resulting complexes Gd‐DOTA‐NOx Eu‐DOTA‐NOx stable compounds in aqueous solution. NMR‐spectroscopic characterization revealed high excess twisted square antiprismatic (TSAP) coordination geometry over (SAP). was found be r 1 =7.7 m −1 s (1.41 T, 37 °C), unusually value comparable weight. We attribute steric influence ordering effect on outer sphere water molecules surrounding generated by strongly hydrated groups. Moreover, against transchelation EDTA (200 eq) period 36 h, it has similar vitro cell toxicity as clinically used DOTA‐based GBCAs.

Language: Английский

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Interaction of Grafted Polymeric N-oxides with Charged Dyes

Langmuir, Journal Year: 2025, Volume and Issue: unknown

Published: April 24, 2025

Grafted polymeric N-oxides have recently attracted interest for antifouling applications, drug delivery, wastewater purification, and electronic devices. Their function depends on the efficiency of grafting process following postgrafting oxidation step. These two parameters govern solvent-accessible charge density surface, an important parameter, which is notoriously hard to determine. In this study, a novel colorimetric quantitative assay was developed. It allows determination surface grafted N-oxides. The method based adsorption acid fuchsin (AF) through reversible electrostatic interactions between positively charged nitrogen atoms N-oxide functionality sulfonate groups dye. thus pH-switchable properties Adsorption achieved at pH value 3, where are almost fully protonated (typical pKa 4-5). AF desorbed from 7 quantified via visible spectroscopy (UV-vis) 556 nm determine amount surface-grafted functional groups. Charge densities diverse by free radical polymerization polyethylene (PE) were determined be in range 1-3 × 1015 N+-O-/cm2. Notably, can form covalent bonds with electron-deficient triarylmethane dyes like AF. This nucleophilic reactivity does not compromise proposed assay, but it may relevance dye desorption purification.

Language: Английский

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Iodinated PSMA Ligands as XFI Tracers for Targeted Cell Imaging and Characterization of Nanoparticles

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 11880 - 11880

Published: Nov. 5, 2024

Prostate cancer is the second most commonly diagnosed in men worldwide. Despite this, current diagnostic tools are still not satisfactory, lacking sensitivity for early-stage or single-cell diagnosis. This study describes development of small-molecule tracers well-known tumor marker prostate-specific membrane antigen (PSMA). These contain a urea motif PSMA-targeting and iodinated aromatic moieties to allow detection via X-ray fluorescence imaging (XFI). Tracers with triiodobenzoyl moiety allowed specific targeting successful PSMA+ cell lines XFI. The XFI-measured uptake 7.88 × 10

Language: Английский

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Three Is a Magic Number: Tailored Clickable Chelators Used to Determine Optimal RGD-Peptide Multiplicity in αvβ6-Integrin Targeted ¹⁷⁷Lu-Labeled Cancer Theranostics

Bioconjugate Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 28, 2024

The cellular adhesion receptor αvβ6-integrin is highly expressed in many cancers, e.g., pancreatic, lung, head-and-neck, cervical, bladder, and esophageal carcinoma. Multimerization of αvβ6-integrin-specific RGD peptides increases the target affinity retention but affects biodistribution pharmacokinetics. Amide formation terminal carboxylic acid moieties square-symmetrical bifunctional chelator DOTPI with 3-azidopropylamine yields derivatives 4, 3, 2 azides zero, 1, remaining acids, respectively, whereby 2-cis-isomer preferred according to NMR investigation Eu(III)-complexes. Cu(II)-catalyzed alkyne-azide cycloaddition (CuAAC) alkyne-functionalized binding peptide cyclo[YRGDLAYp(

Language: Английский

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