Synthesis and evaluation of α-halogenated analogues of 3-(acetylhydroxyamino)propylphosphonic acid (FR900098) as antimalarials

Three alpha-halogenated analogues of 3-(acetylhydroxyamino)propylphosphonic acid (FR900098) have been synthesized from diethyl but-3-enylphosphonate using a previously described method for the alpha-halogenation of alkylphosphonates. These analogues were evaluated for antimalarial potential in vitro against Plasmodium falciparum and in vivo in the P. berghei mouse model. All three analogues showed higher in vitro and/or in vivo potency than the reference compounds

The label matters : µPET imaging of the biodistribution of low molar mass 89Zr and 18F-labeled poly(2-ethyl-2-oxazoline)

Poly(2-alkyl-2-oxazoline)s (PAOx) have received increasing interest for biomedical applications. Therefore, it is of fundamental importance to gain an in-depth understanding of the biodistribution profile of PAOx. We report the biodistribution of poly(2-ethyl-2-oxazoline) (PEtOx) with a molar mass of 5 kDa radiolabeled with PET isotopes Zr-89 and F-18. F-18-labeled PEtOx is prepared by the strain-promoted azide-alkyne cycloaddition (SPAAC) of [F-18]fluoroethylazide to bicyclo[6.1.0]non-4-yne (BCN)-functionalized PEtOx as many common labeling strategies were found to be unsuccessful for PEtOx. Zr-89-labeled PEtOx is prepared using desferrioxamine end-groups as a chelator. Five kDa PEtOx shows a significantly faster blood clearance compared to PEtOx of higher molar mass while uptake in the liver is lower, indicating a minor contribution of the liver in excretion of the 5 kDa PEtOx. While [F-18]-PEtOx displays a rapid and efficient clearance from the kidneys, 5 kDa [Zr-89]-Df-PEtOx is not efficiently cleared over the time course of the study, which is most likely caused by trapping of Zr-89-labeled metabolites in the renal tubules and not the polymer itself, demonstrating,the importance of selecting the appropriate label for biodistribution studies