Synthesis and heme-binding correlation with antimalarial activity of 3,6-bis-(omega-N,N-diethylaminoamyloxy)-4,5-difluoroxanthone.
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.
Dodean
Rozalia A
RA
Department of Chemistry, Portland State University, Portland, OR 97207, USA.
Kelly
Jane X
JX
Peyton
David
D
Gard
Gary L
GL
Riscoe
Michael K
MK
Winter
Rolf W
RW
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D005461:Fluorine / Q000737:chemistry; D006418:Heme / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000187:drug effects; D013053:Spectrophotometry; D013329:Structure-Activity Relationship; D044004:Xanthones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
C528330:3,6-bis-(omega-N,N-diethylaminoamyloxy)-4,5-difluoroxanthone; D000962:Antimalarials; D044004:Xanthones; D005461:Fluorine; D006418:Heme