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Antimalarial activity of ruthenium(ii) and osmium(ii) arene complexes with mono- and bidentate chloroquine analogue ligands.

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Author

  • Erik Ekengard
  • Lotta Glans
  • Irwin Cassells
  • Thibault Fogeron
  • Preshendren Govender
  • Tameryn Stringer
  • Prinessa Chellan
  • George C Lisensky
  • William H Hersh
  • Isa Doverbratt
  • Sven Lidin
  • Carmen de Kock
  • Peter J Smith
  • Gregory S Smith
  • Ebbe Nordlander
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Summary, in English

Eight new ruthenium and five new osmium p-cymene half-sandwich complexes have been synthesized, characterized and evaluated for antimalarial activity. All complexes contain ligands that are based on a 4-chloroquinoline framework related to the antimalarial drug chloroquine. Ligands are salicylaldimine derivatives, where = N-(2-((2-hydroxyphenyl)methylimino)ethyl)-7-chloroquinolin-4-amine, and contain non-hydrogen substituents in the 3-position of the salicylaldimine ring, viz. F, Cl, Br, I, NO2, OMe and (t)Bu for , respectively. Ligand is also a salicylaldimine-containing ligand with substitutions in both 3- and 5-positions of the salicylaldimine moiety, i.e. N-(2-((2-hydroxy-3,5-di-tert-butylphenyl)methyl-imino)ethyl)-7-chloroquinolin-4-amine, while is N-(2-((1-methyl-1H-imidazol-2-yl)methylamino)ethyl)-7-chloroquinolin-4-amine) The half sandwich metal complexes that have been investigated are [Ru(η(6)-cym)()Cl] (Ru--Ru-, cym = p-cymene), [Os(η(6)-cym)()Cl] (Os--Os-, Os-, and Os-), [M(η(6)-cym)()Cl2] (M = Ru, Ru-; M = Os, Os-) and [M(η(6)-cym)()Cl]Cl (M = Ru, Ru-; M = Os, Os-). In complexes Ru--Ru- and Ru-, Os--Os-, Os- and Os- and Os-, the ligands were found to coordinate as bidentate N,O- and N,N-chelates, while in complexes Ru- and Os-, monodentate coordination of the ligands through the quinoline nitrogen was established. The antimalarial activity of the new ligands and complexes was evaluated against chloroquine sensitive (NF54 and D10) and chloroquine resistant (Dd2) Plasmodium falciparum malaria parasite strains. Coordination of ruthenium and osmium arene moieties to the ligands resulted in lower antiplasmodial activities relative to the free ligands, but the resistance index is better for the ruthenium complexes compared to chloroquine. Overall, osmium complexes appeared to be less active than the corresponding ruthenium complexes.

Publishing year

2015

Language

English

Pages

19314-19329

Publication/Series

Dalton Transactions

Volume

44

Issue

44

Document type

Journal article

Publisher

Royal Society of Chemistry

Topic

  • Medicinal Chemistry

Status

Published

ISBN/ISSN/Other

  • ISSN: 1477-9234