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

被引：54

作者：

Ekengard, Erik ^{[1
]}

Glans, Lotta ^{[1
]}

Cassells, Irwin ^{[2
]}

Fogeron, Thibault ^{[1
]}

Govender, Preshendren ^{[2
]}

Stringer, Tameryn ^{[2
]}

Chellan, Prinessa ^{[2
]}

Lisensky, George C. ^{[3
]}

Hersh, William H. ^{[4
,5
]}

Doverbratt, Isa ^{[6
]}

Lidin, Sven ^{[6
]}

de Kock, Carmen ^{[7
]}

Smith, Peter J. ^{[7
]}

Smith, Gregory S. ^{[2
]}

Nordlander, Ebbe ^{[1
]}

机构：

[1] Lund Univ, Dept Chem, Inorgan Chem Res Grp, Chem Phys, SE-22100 Lund, Sweden

[2] Univ Cape Town, Dept Chem, Private Bag, ZA-7701 Rondebosch, South Africa

[3] Beloit Coll, Dept Chem, Beloit, WI 53511 USA

[4] CUNY, Queens Coll, Dept Chem & Biochem, Queens, NY 11367 USA

[5] CUNY, Grad Ctr, Queens, NY 11367 USA

[6] Lund Univ, Dept Chem, Ctr Anal & Synth, SE-22100 Lund, Sweden

[7] Univ Cape Town, Sch Med, Dept Med, Div Pharmacol, ZA-7925 Observatory, South Africa

来源：

DALTON TRANSACTIONS | 2015年 / 44卷 / 44期

基金：

新加坡国家研究基金会; 英国医学研究理事会;

关键词：

POTENT ANTICANCER ACTIVITY; CANCER-CELL CYTOTOXICITY; IN-VITRO ANTIMALARIAL; CRYSTAL-STRUCTURES; PLASMODIUM-FALCIPARUM; BIOLOGICAL-ACTIVITY; HYDROXAMIC ACID; MALARIA; CHEMOTHERAPY; RESISTANCE;

D O I：

10.1039/c5dt02410b

中图分类号：

O61 [无机化学];

学科分类号：

070301 ; 081704 ;

摘要：

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 Bu-t 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(eta(6)-cym)(L1-8)Cl] (Ru-1-Ru-8, cym = p-cymene), [Os(eta(6)-cym)(L-1-3,L-5,L-7)Cl] (Os-1-Os-3, Os-5, and Os-7), [M(eta(6)-cym)(HL9)Cl-2] (M = Ru, Ru-HL9; M = Os, Os-HL9) and [M(eta(6)-cym)(L-10)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.

引用

页码：19314 / 19329

页数：16

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