title: Synthesis, characterization and antimalarial activity of new chromium arene-quinoline half sandwich complexes.
abstract: Organometallic analogs of chloroquine (CQ) are of interest as drug candidates that may be able to overcome the widespread chloroquine resistance developed by malaria parasites. Two new chromium arene CQ-analogs: [η(6)-N-(7-chloroquinolin-4-yl)-N'-(2-dimethylamino-methylbenzyl)-ethane-1,2-diamine]tricarbonylchromium 4 and [η(6)-N-(7-chloroquinolin-4-yl)-N'-(2-dimethylaminobenzyl)-ethane-1,2-diamine]tricarbonylchromium 9 have been synthesized and characterized. In addition, X-ray crystal structures of the intermediates (η(6)-benzyldimethylamine)tricarbonylchromium 2, [η(6)-2-((dimethylamino)methyl) benzaldehyde]tricarbonylchromium 3 and p-(η(6)-dimethylaminobenzaldehyde)tricarbonyl chromium 8 are reported. Compound 4 was more active than chloroquine against both CQ-sensitive and CQ-resistant strains of Plasmodium falciparum when antimalarial activity was tested in vitro. The activity of 4 against the CQ-resistant parasite strain was twice as high as for the organic ligand alone (IC(50) values of 33.9 nM versus 63.1 nM).
authors.affiliation: Inorganic Chemistry Research Group, Chemical Physics, Center for Chemistry and Chemical Engineering, Lund University, Lund, Sweden.
authors.forename: Lotta
authors.initials: L
authors.lastname: Glans
authors.forename: Dale
authors.initials: D
authors.lastname: Taylor
authors.forename: Carmen
authors.initials: C
authors.lastname: de Kock
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Smith
authors.forename: Matti
authors.initials: M
authors.lastname: Haukka
authors.forename: John R
authors.initials: JR
authors.lastname: Moss
authors.forename: Ebbe
authors.initials: E
authors.lastname: Nordlander
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002857:Chromium / Q000737:chemistry*; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D020128:Inhibitory Concentration 50; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C561427:(eta6-N-(7-chloroquinolin-4-yl)-N'-(2-dimethylaminomethylbenzyl)ethane-1,2-diamine)tricarbonylchromium(0); D000962:Antimalarials; D056831:Coordination Complexes; D009942:Organometallic Compounds; D011804:Quinolines; D002857:Chromium