title: Copper chelating anti-inflammatory agents; N1-(2-aminoethyl)-N2-(pyridin-2-ylmethyl)-ethane-1,2-diamine and N-(2-(2-aminoethylamino)ethyl)picolinamide: an in vitro and in vivo study.
abstract: An in vitro and in vivo study of some copper chelating anti-inflammatory agents for alleviation of inflammation associated with rheumatoid arthritis (RA) has been conducted. Two copper chelating agents, N(1)-(2-aminoethyl)-N(2)-(pyridin-2-ylmethyl)ethane-1,2-diamine ([555-N]) and N-(2-(2-aminoethylamino)ethyl)picolinamide ([H(555)-N]) have been synthesized as their hydrochloride salt; their protonation constants and formation constants with Cu(II), Zn(II) and Ca(II) determined by glass electrode potentiometry at 298K and an ionic strength of 0.15M. Cu(II) formed stable complexes at physiological pH while the in vivo competitors, Zn(II) and Ca(II) formed weak complexes with both chelating agents. Both [555-N] and [H(555)-N] showed better selectivity for Cu(II) than for Zn(II) and Ca(II). Electronic spectra for species formed at physiological pH suggest a square planar geometry. Speciation calculations using a blood plasma model predicted that these copper chelating agents are able to mobilize Cu(II) in vivo, while bio-distribution studies of their (64)Cu(II)-labelled complexes at physiological pH showed tissue accumulation and retention indicating an encouraging biological half life.
authors.affiliation: University of Cape Town, Department of Chemistry, P/Bag Rondebosch 7701, South Africa.
authors.forename: John N
authors.initials: JN
authors.lastname: Zvimba
authors.forename: Graham E
authors.initials: GE
authors.lastname: Jackson
mesh_terms: D000577:Amides / Q000737:chemistry* / Q000493:pharmacokinetics; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000493:pharmacokinetics; D002614:Chelating Agents / Q000737:chemistry* / Q000493:pharmacokinetics; D003300:Copper / Q000737:chemistry*; D005021:Ethylamines / Q000737:chemistry* / Q000493:pharmacokinetics; D006863:Hydrogen-Ion Concentration; D009994:Osmolar Concentration; D010848:Picolinic Acids / Q000737:chemistry* / Q000493:pharmacokinetics; D011725:Pyridines / Q000737:chemistry* / Q000493:pharmacokinetics; D013056:Spectrophotometry, Ultraviolet; D014018:Tissue Distribution
chemical_list: D000577:Amides; D000893:Anti-Inflammatory Agents; D002614:Chelating Agents; D005021:Ethylamines; C518377:N-(2-(2-aminoethylamino)ethyl)picolinamide; C518375:N1-(2-aminoethyl)-N2-(pyridin-2-ylmethyl)-ethane-1,2-diamine; D010848:Picolinic Acids; D011725:Pyridines; D003300:Copper