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

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• 作者：Lotta Glans^a ; Dale Taylor^b ; Carmen de Kock^b ; Peter J. Smith^b ; Matti Haukka^c ; John R. Moss^d ; ^† ; ; Ebbe Nordlander^a ; ^{Ebbe.Nordlander@chemphys.lu.se"" rel=""nofollow}
• 关键词：Bioorganometallic chemistry ; Chromium ; Antimalarial ; Chloroquine
• 刊名：Journal of Inorganic Biochemistry
• 出版年：2011
• 出版时间：July 2011
• 年：2011
• 卷：105
• 期：7
• 页码：985-990
• 全文大小：486 K

文摘

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: [η⁶-N-(7-chloroquinolin-4-yl)-N′-(2-dimethylamino-methylbenzyl)-ethane-1,2-diamine]tricarbonylchromium 4 and [η⁶-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 (η⁶-benzyldimethylamine)tricarbonylchromium 2, [η⁶-2-((dimethylamino)methyl) benzaldehyde]tricarbonylchromium 3 and p-(η⁶-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 (IC₅₀ values of 33.9 nM versus 63.1 nM).