Search: onr:"swepub:oai:DiVA.org:uu-252687" >
Synthesis and Bioac...
Synthesis and Bioactivity of beta-Substituted Fosmidomycin Analogues Targeting 1-Deoxy-D-xylulose-5-phosphate Reductoisomerase
-
Chofor, Rene (author)
-
- Sooriyaarachchi, Sanjeewani (author)
- Uppsala universitet,Struktur- och molekylärbiologi,Science for Life Laboratory, SciLifeLab
-
Risseeuw, Martijn D. P. (author)
-
show more...
-
- Bergfors, Terese (author)
- Uppsala universitet,Struktur- och molekylärbiologi,Science for Life Laboratory, SciLifeLab
-
Pouyez, Jenny (author)
-
Johny, Chinchu (author)
-
Haymond, Amanda (author)
-
Everaert, Annelien (author)
-
Dowd, Cynthia S. (author)
-
Maes, Louis (author)
-
Coenye, Tom (author)
-
Alex, Alexander (author)
-
Couch, Robin D. (author)
-
- Jones, T. Alwyn (author)
- Uppsala universitet,Struktur- och molekylärbiologi,Science for Life Laboratory, SciLifeLab
-
Wouters, Johan (author)
-
- Mowbray, Sherry L. (author)
- Uppsala universitet,Struktur- och molekylärbiologi,Science for Life Laboratory, SciLifeLab
-
Van Calenbergh, Serge (author)
-
show less...
-
(creator_code:org_t)
- 2015-03-31
- 2015
- English.
-
In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 58:7, s. 2988-3001
- Related links:
-
https://uu.diva-port... (primary) (Raw object)
-
show more...
-
https://repository.u...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- Blocking the 2-C-methyl-d-erythrithol-4-phosphate (MEP) pathway for isoprenoid biosynthesis offers interesting prospects for inhibiting Plasmodium or Mycobacterium spp. growth. Fosmidomycin (1) and its homologue FR900098 (2) potently inhibit 1-deoxy-d-xylulose-5-phosphate reductoisomerase (Dxr), a key enzyme in this pathway. Here we introduced aryl or aralkyl substituents at the beta-position of the hydroxamate analogue of 2. While direct addition of a beta-aryl moiety resulted in poor inhibition, longer linkers between the carbon backbone and the phenyl ring were generally associated with better binding to the enzymes. X-ray structures of the parasite Dxr-inhibitor complexes show that the longer compounds generate a substantially different flap structure, in which a key tryptophan residue is displaced, and the aromatic group of the ligand lies between the tryptophan and the hydroxamates methyl group. Although the most promising new Dxr inhibitors lack activity against Escherichia coli and Mycobacterium smegmatis, they proved to be highly potent inhibitors of Plasmodium falciparum in vitro growth.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Läkemedelskemi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medicinal Chemistry (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
-
Chofor, Rene
-
Sooriyaarachchi, ...
-
Risseeuw, Martij ...
-
Bergfors, Terese
-
Pouyez, Jenny
-
Johny, Chinchu
-
show more...
-
Haymond, Amanda
-
Everaert, Anneli ...
-
Dowd, Cynthia S.
-
Maes, Louis
-
Coenye, Tom
-
Alex, Alexander
-
Couch, Robin D.
-
Jones, T. Alwyn
-
Wouters, Johan
-
Mowbray, Sherry ...
-
Van Calenbergh, ...
-
show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Basic Medicine
-
and Medicinal Chemis ...
- Articles in the publication
-
Journal of Medic ...
- By the university
-
Uppsala University