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Design, synthesis, and antiprotozoal evaluation of new 2,9‐bis[(substituted‐aminomethyl)phenyl]‐1,10‐phenanthroline derivatives.
- Source :
-
Chemical Biology & Drug Design . May2018, Vol. 91 Issue 5, p974-995. 25p. - Publication Year :
- 2018
-
Abstract
- A series of new 2,9‐bis[(substituted‐aminomethyl)phenyl]‐1,10‐phenanthroline derivatives was synthesized, and the compounds were screened in vitro against three protozoan parasites (<italic>Plasmodium falciparum</italic>,<italic> Leishmania donovani</italic>, and <italic>Trypanosoma brucei brucei</italic>). Biological results showed antiparasitic activity with IC50 values in the μ m range. The in vitro cytotoxicity of these molecules was assessed by incubation with human HepG2 cells; for some derivatives, cytotoxicity was observed at significantly higher concentrations than antiparasitic activity. The 2,9‐bis[(substituted‐aminomethyl)phenyl]‐1,10‐phenanthroline <bold>1h</bold> was identified as the most potent antimalarial candidate with ratios of cytotoxic‐to‐antiparasitic activities of 107 and 39 against a chloroquine‐sensitive and a chloroquine‐resistant strain of <italic>P. falciparum</italic>, respectively. As the telomeres of the parasite <italic>P. falciparum</italic> are the likely target of this compound, we investigated stabilization of the Plasmodium telomeric G‐quadruplexes by our phenanthroline derivatives through a FRET melting assay. The ligands <bold>1f</bold> and <bold>1m</bold> were noticed to be more specific for FPf8T with higher stabilization for FPf8T than for the human F21T sequence. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 17470277
- Volume :
- 91
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- Chemical Biology & Drug Design
- Publication Type :
- Academic Journal
- Accession number :
- 129102874
- Full Text :
- https://doi.org/10.1111/cbdd.13164