title: Re and (99m)Tc organometallic complexes containing pendant l-arginine derivatives as potential probes of inducible nitric oxide synthase.
abstract: Aiming to design radioactive compounds based on the core "(99m)Tc(CO)(3)" for probing inducible nitric oxide synthase (iNOS) levels in vivo, we have synthesized conjugates containing a pyrazolyl-diamine chelating unit and pendant l-arginine analogues (substrates and inhibitors of NOS). Reaction of the conjugates with fac-[M(CO)(3)](+) (M = Re, (99m)Tc) gave bioorganometallic complexes of the type fac-[M(CO)(3)(k(3)-L)] in good yield. After in vitro testing using the oxyhemoglobin NO capture assay, we concluded that the affinity of the inhibitor-containing conjugates to iNOS seems to be less affected upon metallation with rhenium than the substrate-containing conjugates. The complexes bearing guanidino substituted analogues of l-arginine still present considerable inhibitory action (N(omega)-monomethyl-l-arginine, K(i) = 36 microM; N(omega)-nitro-l-arginine, K(i) = 84 microM), being the first examples of organometallic complexes able to inhibit the iNOS. These results seem to indicate that (99m)Tc(CO)(3)-labeled L-argininine analogues, namely NOS inhibitors, may hold potential for monitoring increased levels of iNOS in vivo.
authors.affiliation: Departamento de Química, ITN, Estrada Nacional 10, 2686-953, Sacavém, Portugal.
authors.forename: Bruno L
authors.initials: BL
authors.lastname: Oliveira
authors.forename: João D G
authors.initials: JD
authors.lastname: Correia
authors.forename: Paula D
authors.initials: PD
authors.lastname: Raposinho
authors.forename: Isabel
authors.initials: I
authors.lastname: Santos
authors.forename: António
authors.initials: A
authors.lastname: Ferreira
authors.forename: Carlos
authors.initials: C
authors.lastname: Cordeiro
authors.forename: Ana P
authors.initials: AP
authors.lastname: Freire
mesh_terms: D001120:Arginine / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D015335:Molecular Probes; D052247:Nitric Oxide Synthase Type II / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry*; D015609:Organotechnetium Compounds / Q000737:chemistry*; D012211:Rhenium / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet
chemical_list: D015335:Molecular Probes; D009942:Organometallic Compounds; D015609:Organotechnetium Compounds; D012211:Rhenium; D001120:Arginine; D052247:Nitric Oxide Synthase Type II