Enantiomerization and enantioselective bioaccumulation of diclofop-methyl in tubifex worms.

In this study, the hydrolysis of diclofop-methyl (DM) in aqueous system and the bioaccumulation of its main metabolite, Diclofop (DA), in the tubifex worms were investigated using enantioselective high-performance liquid chromatography. With the addition of tubifex, rapid hydrolysis was observed for DM. It is revealed that the hydrolysis of DM in the water and the accumulation of DA in the worms were both enantioselective. Meanwhile, either the hydrolysis amount or the levels of enantioselectivity were influenced by the tubifex. After incubated for 24 h, about 94.6% of the DM was hydrolyzed and the enantiomer fraction of metabolite (DA) deviated from 0.5 with R-DA significantly higher than S-DA. The enantiopure S-DM and R-DM and S-DA and R-DA were incubated, and enantiomerizations were detected between the two DM enantiomers with S-form inversing into R-form and vice versa. It was found that the S-DM exhibited a higher tendency to invert than the R-DM.

Novel imaging agents for ß-amyloid plaque based on the N-benzoylindole core.

We report the synthesis and evaluation of a series of N-benzoylindole derivatives as novel potential imaging agents for ß-amyloid plaques. In vitro binding studies using Aß(1-40) aggregates versus [(125)I]TZDM showed that all these derivatives demonstrated high binding affinities (K(i) values ranged from 8.4 to 121.6 nM). Moreover, two radioiodinated compounds [(125)I]7 and [(125)I]14 were prepared. Autoradiography for [(125)I]14 displayed intense and specific labeling of Aß plaques in the brain sections of AD model mice (C57, APP/PS1) with low background. In vivo biodistribution in normal mice exhibited sufficient initial brain uptake for imaging (2.19% and 2.00%ID/g at 2 min postinjection for [(125)I]7 and [(125)I]14, respectively). Although additional modifications are necessary to improve brain uptake and clearance from the brain, the N-benzoylindole may be served as a backbone structure to develop novel ß-amyloid imaging probes.

Novel anilinophthalimide derivatives as potential probes for beta-amyloid plaque in the brain.

A group of novel 4,5-dianilinophthalimide derivatives has been synthesized in this study for potential use as beta-amyloid (Abeta) plaque probes. Staining of hippocampus tissue sections from Alzheimer's disease (AD) brain with the representative compound 9 indicated selective labeling of it to Abeta plaques. The binding affinity of radioiodinated [(125)I]9 for AD brain homogenates was 0.21 nM (K(d)), and of other derivatives ranged from 0.9 to 19.7 nM, except for N-methyl-4,5-dianilinophthalimide (K(i)>1000 nM). [(125)I]9 possessed the optimal lipophilicity with LogP value of 2.16, and its in vivo biodistribution in normal mice exhibited excellent initial brain uptake (5.16% ID/g at 2 min after injection) and a fast washout rate (0.56% ID/g at 60 min). The encouraging results suggest that this novel derivative of [(123)I]9 may have potential as an in vivo SPECT probe for detecting amyloid plaques in the brain.

Synthesis and biodistribution of two novel 99mTc( SNN/S) "3+1" mixed ligand complexes as potential brain perfusion agents.

Two novel [99mTc] [ SNN/S] "3+1" mixed ligand complexes, where L3H2= o-methylthio-glycinanilide (A) or N-(1-methylthio-phenyl)-ethylenediamine (B) and L1H= isopropanethiol, were synthesized using stannous chloride as reductant and glucoheptonate as transfer ligand. The identifications of [99mTc]-A and [99mTc]-B were established by thin layer chromatography. The radiochemical purity of both complexes was over 90%. The initial biodistribution study in mice demonstrated that both complexes can penetrate the intact blood-brain barrier and exhibit retention in mice brain. The brain uptake (%ID/g) values of [99mTc]-A were 1.68, 1.23, 1.24 and of [99mTc]-B were 1.76, 1.08, 0.90 at 2, 30 and 60 min i.v. postinjection, respectively.