Thiosemicarbazonate Complexes with Affinity for amyloid-β Fibers: Synthesis, Characterization and Biological Studies

Abstract

Aim: Obtain radioimages of amyloid-β fibers using ^99mTc-complexes. Methodology: Tridentate thiosemicarbazone and thiocarbonohydrazone ligands containing fragments (stilbene, azobenzene, benzothiazole or benzoxazole) with affinity for amyloid-ß fibers and its Re(I) complexes have been prepared. The molecular structures of several ligands and complexes were determined by x-ray diffraction. Binding affinity studies toward Aß_1-42 fibers were performed for the ligands and Re(I) complexes. The ability of formation of some ^99mTc(I) complexes, their biodistribution and in vivo stability have been established. Results & conclusion: Complexes of stilbene and benzothiazole thiosemicarbazonates show similar affinity for amyloid-β fibers to the free ligand. These ^99mTc complexes present a reasonable in vivo stability and a low capability to cross the blood–brain barrier although not sufficient to brain amyloid imaging.

Keywords: :

• amyloid
• radiopharm
• rhenium
• technetium
• thiosemicarbazone

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at:www.tandfonline.com/doi/full/10.2217/epi-2016-0184

Acknowledgments

We thank M Pereira da Costa for her collaboration in the radiolabeling studies with ^99mTc.

Financial & competing interests disclosure

This study was supported by European Regional Development Fund, ERDF (EU), Ministerio de Economía y Competitividad, MINECO (Spain) and Fundação para a Ciência e a Tecnologia, FCT (Portugal) under research projects CTQ2015-70901-R, CTQ2017-90802-REDT and UID/Multi/04349/2013. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.