First organometallic inhibitors for human thymidine kinase: synthesis and in vitro evaluation of rhenium(I)- and technetium(I)-tricarbonyl complexes of thymidine

Synthesis, Cytotoxicity, and Insight into the Mode of Action of Re(CO)3 Thymidine Complexes

“…The metal precursor [Re(CO) 3 (H 2 O) 3 ]Br was prepared according to published procedures. [19] Reactions were monitored by thin-layer chromatography using precoated silica gel 60 F 254 aluminum sheets (Merck) and precoated alumina oxide 60 F 254 PET foils (Sigma) visualized by UV irradiation. Column chromatography was performed using silica gel 60 (MP Biomedicals GmbH, Germany) and alumina oxide 58 (Alfa Aesar, activated, basic, Brockmann Grade I).…”

“…Compound 18 was prepared by a procedure similar to that described for compound 11, except that compound 7 was used instead of compound 5. After the aqueous workup, the crude product was further purified by silica gel chromatography using a gradient of (19). Compound 19 was prepared by a procedure similar to that described for compound 11, except that compound 8 was used instead of compound 5.…”

“…[17,18] This latter application has led to considerable interest in the [M(CO) 3 ] + 1 core with M = 99m Tc or Re. [19][20][21][22][23] The corresponding technetium and rhenium precursors [M(CO) 3 (H 2 O) 3 ] + 1 can be conveniently accessed by synthetic procedures, are water soluble, and the three aqua ligands are labile and can readily undergo ligand exchange. [24][25][26] The [M(CO) 3 ] + 1 core is chemically robust, and complexes are chemically inert because of the d 6 low-spin electronic configuration, thus maintaining their integrity under the most forcing conditions.…”

Estudos in vitro e in vivo de análogo da timidina marcada com complexo organometálico de tecnécio-99m para potencial uso em diagnóstico tumoral

“…A conjugação de agentes quelantes na timidina em outra posição se não a 5' da pentose, pode proporcionar a redução das ligações da enzima TQ 1 (Schibli et al, 2003) . No entanto, é nesta posição que ocorre a fosforilação da timidina, a qual inicia o seu metabolismo até a incorporação no DNA (Lodish et al, 2002).…”

“…2) foi sintetizado pelo Centro de Radiofarmácia do Paul Scherrer Institute, Villigen, Suíça de acordo com a literatura (Schibli et al, 2003). O pertecnetato de sódio foi eluído em 6 mL em solução A marcação foi realizada com 50 μg do ligante L (onde L = timidina-ácido aminodiacético) e 350 μL do precursor carbonil-tecnécio-99m, previamente preparado.…”