| 1. |
- Ekengard, Erik, et al.
(författare)
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Antimalarial activity of ruthenium(ii) and osmium(ii) arene complexes with mono- and bidentate chloroquine analogue ligands.
- 2015
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Ingår i: Dalton Transactions. - : Royal Society of Chemistry (RSC). - 1477-9234 .- 1477-9226. ; 44:44, s. 19314-19329
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Stringer, Tameryn, et al.
(författare)
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Evaluation of PTA-derived ruthenium(II) and iridium(III) quinoline complexes against chloroquine-sensitive and resistant strains of the Plasmodium falciparum malaria parasite
- 2019
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Ingår i: Journal of Inorganic Biochemistry. - : Elsevier BV. - 0162-0134. ; 191, s. 164-173
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Tidskriftsartikel (refereegranskat)abstract
- Cationic 1,3,5‑triaza‑phosphaadamantane (PTA) quinoline ruthenium(II) and iridium(III) complexes were successfully synthesized and characterized using standard spectroscopic and analytical techniques. The complexes were evaluated for their in vitro antiplasmodial activities against the chloroquine-sensitive (CQS) NF54 and chloroquine-resistant (CQR) K1 strains of the Plasmodium falciparum species of the malaria parasite and were found to exhibit good activities in the sensitive strain but moderate activities in the resistant strain, suggesting a resistance mechanism similar to chloroquine (CQ). Selected samples were screened for their ability to inhibit synthetic haemozoin formation and were found to be inhibitors with similar activity to CQ. The complexes also exhibit moderate to low cytotoxicity when evaluated against the Chinese Hamster Ovarian (CHO) cell-line in vitro, suggesting selectivity towards the malaria parasite rather than mammalian cells.
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