Synthesis, cytotoxicity and antimalarial activity of ferrocenyl amides of 4-aminoquinolines. 2010

David D N'Da, and Jaco C Breytenbach, and Peter J Smith, and Carmen Lategan
Department of Pharmaceutical Chemistry, School Pharmacy, North-West University, Potchefstroom, South Africa. david.nda@nwu.ac.za

Series of 4-aminoquinolines bearing an amino side chain linked to the ferrocene moiety through an amide bond were synthesized and evaluated for their antimalarial activity against both chloroquine-sensitive (D10, CQ-S) and chloroquine-resistant (Dd2, CQ-R) strains of Plasmodium falciparum. They were also tested for cytotoxicity against Chinese Hamster Ovarian (CHO) cells. Amide 12 featuring propyl side chain linked to the ferrocene ring was the most active of all tested compounds. With an IC50 value of 0.08 microg/mL, this amide showed 1.5-fold higher activity than chloroquine diphosphate (IC50 = 0.12 microg/mL) against the resistant strain, with a selectivity index of 550 indicating its high selectivity towards the parasite. Derivatives which were equipotent against both strains also showed up to ten-fold increase in activity compared to primaquine.

UI MeSH Term Description Entries
D007202 Indicators and Reagents Substances used for the detection, identification, analysis, etc. of chemical, biological, or pathologic processes or conditions. Indicators are substances that change in physical appearance, e.g., color, at or approaching the endpoint of a chemical titration, e.g., on the passage between acidity and alkalinity. Reagents are substances used for the detection or determination of another substance by chemical or microscopical means, especially analysis. Types of reagents are precipitants, solvents, oxidizers, reducers, fluxes, and colorimetric reagents. (From Grant & Hackh's Chemical Dictionary, 5th ed, p301, p499) Indicator,Reagent,Reagents,Indicators,Reagents and Indicators
D007928 Lethal Dose 50 The dose amount of poisonous or toxic substance or dose of ionizing radiation required to kill 50% of the tested population. LD50,Dose 50, Lethal
D009682 Magnetic Resonance Spectroscopy Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING). In Vivo NMR Spectroscopy,MR Spectroscopy,Magnetic Resonance,NMR Spectroscopy,NMR Spectroscopy, In Vivo,Nuclear Magnetic Resonance,Spectroscopy, Magnetic Resonance,Spectroscopy, NMR,Spectroscopy, Nuclear Magnetic Resonance,Magnetic Resonance Spectroscopies,Magnetic Resonance, Nuclear,NMR Spectroscopies,Resonance Spectroscopy, Magnetic,Resonance, Magnetic,Resonance, Nuclear Magnetic,Spectroscopies, NMR,Spectroscopy, MR
D010963 Plasmodium falciparum A species of protozoa that is the causal agent of falciparum malaria (MALARIA, FALCIPARUM). It is most prevalent in the tropics and subtropics. Plasmodium falciparums,falciparums, Plasmodium
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D002738 Chloroquine The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses. Aralen,Arechine,Arequin,Chingamin,Chlorochin,Chloroquine Sulfate,Chloroquine Sulphate,Khingamin,Nivaquine,Sulfate, Chloroquine,Sulphate, Chloroquine
D002855 Chromatography, Thin Layer Chromatography on thin layers of adsorbents rather than in columns. The adsorbent can be alumina, silica gel, silicates, charcoals, or cellulose. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Chromatography, Thin-Layer,Thin Layer Chromatography,Chromatographies, Thin Layer,Chromatographies, Thin-Layer,Thin Layer Chromatographies,Thin-Layer Chromatographies,Thin-Layer Chromatography
D003412 Cricetulus A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research. Hamsters, Armenian,Hamsters, Chinese,Hamsters, Grey,Armenian Hamster,Armenian Hamsters,Chinese Hamster,Chinese Hamsters,Grey Hamster,Grey Hamsters,Hamster, Armenian,Hamster, Chinese,Hamster, Grey
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005296 Ferrous Compounds Inorganic or organic compounds that contain divalent iron. Compounds, Ferrous

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