Synthesis, characterization and antimalarial activity of new chromium arene-quinoline half sandwich complexes

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).