ABSTRACT
With the objective to develop a potential 99mTc radiopharmaceutical for imaging the androgen receptor (AR) in prostate cancer, four ligands bearing the same pharmacophore derived from the AR antagonist flutamide were prepared, labeled with 99mTc, and their structures corroborated via comparison with the corresponding stable rhenium analogs. All complexes were obtained with high radiochemical purity. Three of the complexes were highly stable, and, due to their favorable physicochemical properties, were further evaluated using AR-positive and AR-negative cells in culture. All complexes exhibited considerable uptake in AR-positive cells, which could be blocked by an excess of flutamide. The efflux from the cells was moderate. They also showed significantly lower uptakes in AR-negative cells, indicating interactions with the AR receptor. However, the binding affinities were considerably reduced by the coordination to 99mTc, and the complex that exhibited the best biological behavior did not show sufficient specificity towards AR-positive cells.
Subject(s)
Flutamide , Receptors, Androgen , Male , Humans , Flutamide/pharmacology , Diagnostic Imaging , Radiopharmaceuticals/chemistry , Technetium/chemistry , Organotechnetium Compounds/chemistryABSTRACT
Adding value to organic synthesis. Novel imine reductases enable the enantioselective reduction of imines to afford optically active amines. Likewise, novel bioinspired artificial metalloenzymes can perform the same reaction as well. Emerging proof-of-concepts are herein discussed.
Subject(s)
Biocatalysis , Imines/metabolism , Metalloproteins/metabolism , Oxidoreductases/metabolism , Biotin/metabolism , Imines/chemistry , Oxidation-Reduction , Stereoisomerism , Streptavidin/metabolismABSTRACT
The use of oxidoreductases as biocatalysts for the production of a wide number of chiral building blocks is presently a mature (bio-)technology. In this context some industrial applications are currently performed by means of those enzymatic approaches, and new examples are expected to be realized. Moreover, oxidoreductases provide an interesting academic platform to undertake fundamental research in enzymology, to acquire a better understanding on catalytic mechanisms, and to facilitate the development of new biocatalytic applications. Within this area, a wide number of oxidoreductases from genus Candida spp. have been characterized and used as biocatalysts. These enzymes are rather diverse, and are able to carry out many useful reactions, like highly (enantio)selective keto-reductions, (de)racemizations and stereoinversions, and promiscuous catalytic imine reductions. In addition, some Candida spp. dehydrogenases are very useful for regenerating the cofactors, with the aid of sacrificial substrates. Addressing those features, the present paper aims to give an overview of these enzymes, by focusing on practical applications that these biocatalysts can provide. Furthermore, when possible, academic insights on the enzymatic performances will be discussed as well.