TY - JOUR
T1 - Antimalarial activity of ruthenium(ii) and osmium(ii) arene complexes with mono- and bidentate chloroquine analogue ligands
AU - Ekengard, Erik
AU - Glans, Lotta
AU - Cassells, Irwin
AU - Fogeron, Thibault
AU - Govender, Preshendren
AU - Stringer, Tameryn
AU - Chellan, Prinessa
AU - Lisensky, George C.
AU - Hersh, William H.
AU - Doverbratt, Isa
AU - Lidin, Sven
AU - de Kock, Carmen
AU - Smith, Peter J.
AU - Smith, Gregory S.
AU - Nordlander, Ebbe
PY - 2015/9/16
Y1 - 2015/9/16
N2 - 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 HL1–8 are salicylaldimine derivatives, where HL1 = N-(2-((2-hydroxyphenyl)methylimino)ethyl)-7-chloroquinolin-4-amine, and HL2–8 contain non-hydrogen substituents in the 3-position of the salicylaldimine ring, viz. F, Cl, Br, I, NO2, OMe and tBu for HL2–8, respectively. Ligand HL9 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 HL10 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(η6-cym)(L1–8)Cl] (Ru-1–Ru-8, cym = p-cymene), [Os(η6-cym)(L1–3,5,7)Cl] (Os-1–Os-3, Os-5, and Os-7), [M(η6-cym)(HL9)Cl2] (M = Ru, Ru-HL9; M = Os, Os-HL9) and [M(η6-cym)(L10)Cl]Cl (M = Ru, Ru-10; M = Os, Os-10). In complexes Ru-1–Ru-8 and Ru-10, Os-1–Os-3, Os-5 and Os-7 and Os-10, the ligands were found to coordinate as bidentate N,O- and N,N-chelates, while in complexes Ru-HL9 and Os-HL9, 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.
AB - 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 HL1–8 are salicylaldimine derivatives, where HL1 = N-(2-((2-hydroxyphenyl)methylimino)ethyl)-7-chloroquinolin-4-amine, and HL2–8 contain non-hydrogen substituents in the 3-position of the salicylaldimine ring, viz. F, Cl, Br, I, NO2, OMe and tBu for HL2–8, respectively. Ligand HL9 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 HL10 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(η6-cym)(L1–8)Cl] (Ru-1–Ru-8, cym = p-cymene), [Os(η6-cym)(L1–3,5,7)Cl] (Os-1–Os-3, Os-5, and Os-7), [M(η6-cym)(HL9)Cl2] (M = Ru, Ru-HL9; M = Os, Os-HL9) and [M(η6-cym)(L10)Cl]Cl (M = Ru, Ru-10; M = Os, Os-10). In complexes Ru-1–Ru-8 and Ru-10, Os-1–Os-3, Os-5 and Os-7 and Os-10, the ligands were found to coordinate as bidentate N,O- and N,N-chelates, while in complexes Ru-HL9 and Os-HL9, 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.
UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84946594557&partnerID=MN8TOARS
U2 - 10.1039/c5dt02410b
DO - 10.1039/c5dt02410b
M3 - Article
VL - 44
SP - 19314
EP - 19329
JO - Dalton Transactions
JF - Dalton Transactions
SN - 1477-9226
ER -
