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Synthesis, in vitro antimalarial activities and cytotoxicities of amino-artemisinin-ferrocene derivatives.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2018 Feb 01; Vol. 28 (3), pp. 289-292. Date of Electronic Publication: 2017 Dec 26. - Publication Year :
- 2018
-
Abstract
- Novel derivatives bearing a ferrocene attached via a piperazine linker to C-10 of the artemisinin nucleus were prepared from dihydroartemisinin and screened against chloroquine (CQ) sensitive NF54 and CQ resistant K1 and W2 strains of Plasmodium falciparum (Pf) parasites. The overall aim is to imprint oxidant (from the artemisinin) and redox (from the ferrocene) activities. In a preliminary assessment, these compounds were shown to possess activities in the low nM range with the most active being compound 6 with IC <subscript>50</subscript> values of 2.79 nM against Pf K1 and 3.2 nM against Pf W2. Overall the resistance indices indicate that the compounds have a low potential for cross resistance. Cytotoxicities were determined with Hek293 human embryonic kidney cells and activities against proliferating cells were assessed against A375 human malignant melanoma cells. The selectivity indices of the amino-artemisinin ferrocene derivatives indicate there is overall an appreciably higher selectivity towards the malaria parasite than mammalian cells.<br /> (Copyright © 2017. Published by Elsevier Ltd.)
- Subjects :
- Antimalarials chemical synthesis
Antimalarials chemistry
Antimalarials toxicity
Artemisinins chemistry
Cell Line, Tumor
Cell Proliferation drug effects
Cell Survival drug effects
Cytotoxins chemical synthesis
Cytotoxins chemistry
Cytotoxins toxicity
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Ferrous Compounds chemistry
HEK293 Cells
Humans
Metallocenes chemistry
Molecular Structure
Parasitic Sensitivity Tests
Structure-Activity Relationship
Antimalarials pharmacology
Artemisinins pharmacology
Cytotoxins pharmacology
Ferrous Compounds pharmacology
Metallocenes pharmacology
Plasmodium falciparum drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 28
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 29317166
- Full Text :
- https://doi.org/10.1016/j.bmcl.2017.12.057