106626-63-5Relevant academic research and scientific papers
Cell-specific and nuclear targeting with [M(CO)3]+ (M = 99mTc, Re)-based complexes conjugated to acridine orange and bombesin
Agorastos, Nikos,Borsig, Lubor,Renard, Anabelle,Antoni, Philipp,Viola, Giampietro,Spingler, Bernhard,Kurz, Philipp,Alberto, Roger
, p. 3842 - 3852 (2007)
Receptor-specific nuclear targeting requires trifunctional metal complexes. We have synthesized [M(L2-pept)(L1-acr)(CO)3] (pept = peptide: acr = acridine-based agent) in which the fac-[M(CO) 3]+ moicty (1st function, M = 99mTc. Re) couples an acridine-based nuclear-targeting agent (2nd function. L 1-acr) and the specific cell-receptor-binding peptide bombesin (3rd function, L2-pept). The metalmediated coupling is based on the mixed ligand [2+1] principle. The nuclear targeting agents have been derivatised with an isocyanide group for monodentate (L1) and bombesin (BBN) with a bidentate ligand (L2) for complexation to fac-[M(CO)3]+. For nuclear uptake studies, the model complexes [Re(L2)(L 1-acr)(CO)3] (L2 = pyridine-2-carhoxylic acid and pyridine2.4-dicarhoxylic acid) were synthesized and structurally characterized. We selected acridine derivatives as nucleartargeting agents, because they are very good nucleus-staining agents and exhibit strong fluorescence. Despite the bulky metal complexes attached to acridine. all [Re(L2)(L1-acr)(CO)3] showed high accumulation in the nuclei of PC3 and B16F1 cells, as evidenced by fluorescence microscopy. For radio-pharmaceutical purposes, the 99mTc analogues have been prepared and radioactivity distribution confirmed the fluorescence results. Coupling of BBN to L2 gave the receptor-selective complexes [M(L 2-BBN)(L1-acr)(CO)3]. Whereas no internalization was found with B16F1 cells, fluorescence microscopy on PC3 cells bearing the BBN receptor showed high and rapid uptake by receptor-mediated endocytosis into the cytoplasm, but not into the nucleus.
USE OF METAL TRICARBONYL COMPLEXES AS RADIOTHERAPEUTIC CHEMOTOXIC AGENTS
-
Page/Page column 22, (2010/02/11)
The invention relates to the use of metal tricarbonyl compounds of the general formula [M(CO),L,]', wherein M is rhenium or technetium or an isotope thereof and L is a ligand, for the preparation of a medicament for the treatment of cancer that is both radiotherapeutic and chemotoxic when a radioactive metal is used and chemotoxic when cold rhenium or macroscopic amounts of long-lived Tc-99 is used. The medicament is in particular chemotoxic by causing intrastrand linkages in DNA. In a specific embodiment at least one of L is not OH2. The invention further relates to novel compounds of the general formula IM(CO)3XIX2X3]+and their use, wherein M is rhenium or technetium or an isotope thereof and at least one of X1. X2 and X3 is a monodentate ligand; or two of X, X2 and X3 are part of a bidentate ligand and the other one is optionally a monodentate ligand.
Potential Antitumor Agents. 50. In Vivo Solid-Tumor Activity of Derivatives of N-acridine-4-carboxamide
Atwell, Graham J.,Rewcastle, Gordon W.,Baguley, Bruce C.,Denny, William A.
, p. 664 - 669 (2007/10/02)
The synthesis, physicochemical properties, and antitumor activity of a series of N-acridine-4-carboxamides are reported.The compounds bind to DNA by intercalation, but exist under physiological conditions as monocations due to the w
