Synthesis and heme-binding correlation with antimalarial activity of 3,6-bis-(omega-N,N-diethylaminoamyloxy)-4,5-difluoroxanthone

Rozalia A Dodean; Jane X Kelly; David Peyton; Gary L Gard; Michael K Riscoe; Rolf W Winter

doi:10.1016/j.bmc.2007.10.083

Synthesis and heme-binding correlation with antimalarial activity of 3,6-bis-(omega-N,N-diethylaminoamyloxy)-4,5-difluoroxanthone

Bioorg Med Chem. 2008 Feb 1;16(3):1174-83. doi: 10.1016/j.bmc.2007.10.083. Epub 2007 Nov 26.

Authors

Rozalia A Dodean¹, Jane X Kelly, David Peyton, Gary L Gard, Michael K Riscoe, Rolf W Winter

Affiliation

¹ Department of Chemistry, Portland State University, Portland, OR 97207, USA.

PMID: 18023189
DOI: 10.1016/j.bmc.2007.10.083

Abstract

In this study, the effect of fluorine upon the heme-binding ability of the xanthone nucleus was investigated for 3,6-bis-(omega-N,N-diethylaminoamyloxy)-4,5-difluoroxanthone (F2C5). 2-Fluoro-1,3-dimethoxybenzene was prepared by a new, improved method and used to build up the xanthone nucleus. The interaction of F2C5 with heme was investigated by UV-vis, (1)H NMR, and (19)F NMR spectroscopy. For the first time, NMR studies for the heme-drug interactions are carried out at pH 5.0, physiological for the acidic food vacuole of the malaria parasite.

MeSH terms

Animals
Antimalarials / chemical synthesis*
Antimalarials / chemistry
Antimalarials / pharmacology*
Fluorine / chemistry
Heme / chemistry*
Magnetic Resonance Spectroscopy
Molecular Structure
Plasmodium falciparum / drug effects
Spectrophotometry
Structure-Activity Relationship
Xanthones / chemical synthesis*
Xanthones / chemistry
Xanthones / pharmacology*

Substances

3,6-bis-(omega-N,N-diethylaminoamyloxy)-4,5-difluoroxanthone
Antimalarials
Xanthones
Fluorine
Heme