title: Antimalarial activity of N(6)-substituted adenosine derivatives. Part 3.
abstract: A series of novel 3'-amido-3'-deoxy-N(6)-(1-naphthylmethyl)adenosines was synthesized applying a polymer-assisted solution phase (PASP) protocol and was tested for anti-malarial activity versus the Dd2 strain of Plasmodium falciparum. Further, this series and 62 adenosine derivatives were analyzed regarding 1-deoxy-d-xylulose 5-phosphate (DOXP) reductoisomerase inhibition. Biological evaluations revealed that the investigated 3',N(6)-disubstituted adenosine derivatives displayed moderate but significant activity against the P. falciparum parasite in the low-micromolar range. On the molecular level, DOXP reductoisomerase utilizing an adenosyl-containing substrate was identified as a promising metabolic target for ligands of adenosine binding motifs.
authors.affiliation: Institut für Pharmazie, Abteilung für Pharmazeutische Chemie, Universität Hamburg, Bundesstrasse 45, D-20146 Hamburg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Herforth
authors.forename: Jochen
authors.initials: J
authors.lastname: Wiesner
authors.forename: Philipp
authors.initials: P
authors.lastname: Heidler
authors.forename: Silke
authors.initials: S
authors.lastname: Sanderbrand
authors.forename: Serge
authors.initials: S
authors.lastname: Van Calenbergh
authors.forename: Hassan
authors.initials: H
authors.lastname: Jomaa
authors.forename: Andreas
authors.initials: A
authors.lastname: Link
mesh_terms: D000241:Adenosine / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D019747:Aldose-Ketose Isomerases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology
chemical_list: D000962:Antimalarials; D004791:Enzyme Inhibitors; D009097:Multienzyme Complexes; D010088:Oxidoreductases; C114231:1-deoxy-D-xylulose 5-phosphate reductoisomerase; D019747:Aldose-Ketose Isomerases; D000241:Adenosine