-
Analytical Sciences : the International... Jan 2024NMR screening methods based on F spin-spin relaxation time (F-T) were applied to fluorinated compounds bound to human serum albumin. Diflunisal and fleroxacin (the...
NMR screening methods based on F spin-spin relaxation time (F-T) were applied to fluorinated compounds bound to human serum albumin. Diflunisal and fleroxacin (the fluorinated compounds) contain two and three fluorine atoms per molecule, respectively, and are suitable as the model system for F NMR analysis. It was shown that F-T was more sensitive in monitoring the binding affinity to the target protein than F spin-lattice relaxation time (F-T). The comparisons of F signal intensities acquired at different echo times using F-T pulse sequence were also shown to be an effective means of assessing complex formation for fluorinated compounds.
Topics: Humans; Magnetic Resonance Spectroscopy; Proteins; Fluorine; Serum Albumin, Human; Fleroxacin
PubMed: 37838626
DOI: 10.1007/s44211-023-00435-0 -
Molecules (Basel, Switzerland) Jan 2024The small-molecule iododiflunisal (IDIF) is a transthyretin (TTR) tetramer stabilizer and acts as a chaperone of the TTR-Amyloid beta interaction. Oral administration of...
The small-molecule iododiflunisal (IDIF) is a transthyretin (TTR) tetramer stabilizer and acts as a chaperone of the TTR-Amyloid beta interaction. Oral administration of IDIF improves Alzheimer's Disease (AD)-like pathology in mice, although the mechanism of action and pharmacokinetics remain unknown. Radiolabeling IDIF with positron or gamma emitters may aid in the in vivo evaluation of IDIF using non-invasive nuclear imaging techniques. In this work, we report an isotopic exchange reaction to obtain IDIF radiolabeled with F. [F/F]exchange reaction over IDIF in dimethyl sulfoxide at 160 °C resulted in the formation of [F]IDIF in 7 ± 3% radiochemical yield in a 20 min reaction time, with a final radiochemical purity of >99%. Biodistribution studies after intravenous administration of [F]IDIF in wild-type mice using positron emission tomography (PET) imaging showed capacity to cross the blood-brain barrier (ca. 1% of injected dose per gram of tissue in the brain at t > 10 min post administration), rapid accumulation in the liver, long circulation time, and progressive elimination via urine. Our results open opportunities for future studies in larger animal species or human subjects.
Topics: Humans; Animals; Mice; Pharmaceutical Preparations; Tissue Distribution; Alzheimer Disease; Prealbumin; Amyloid beta-Peptides; Excipients; Diflunisal
PubMed: 38257401
DOI: 10.3390/molecules29020488