MEPicides: α,β-Unsaturated Fosmidomycin Analogues as DXR Inhibitors against Malaria
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چکیده
منابع مشابه
Synthesis and evaluation of ,-unsaturated -aryl-substituted fosmidomycin analogues as DXR inhibitors
Fosmidomycin, which acts through inhibition of 1-deoxy-D-xylulose phosphate reductoisomerase (DXR) in the nonmevalonate pathway, represents a valuable recent addition to the armamentarium against uncomplicated malaria. In this paper we describe the synthesis and biological evaluation of Eand Z-,-unsaturated -aryl-substituted analogues of FR900098, a fosmidomycin congener, utilizing a Stille ...
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The natural antibiotic fosmidomycin acts via inhibition of 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR), an essential enzyme in the non-mevalonate pathway of isoprenoid biosynthesis. Fosmidomycin is active on Mycobacterium tuberculosis DXR (MtDXR), but it lacks antibacterial activity probably because of poor uptake. α-Aryl substituted fosmidomycin analogues have more favorable physicoc...
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Z. Naturforsch. 58b, 106 – 110 (2003); received September 18, 2002 Benzyloxyureas (4) have been prepared by reactions of diethyl 3-benzyloxyamino-propyl-phosphonate (3) with isocyanates, potassium cyanate or 1,1’-carbonyldiimidazole / methylamine. Conversion of phosphonic esters 4 into phosphonic acids 6 by means of bromotrimethylsilane and catalytic hydrogenation of 4, 6 afforded the target co...
متن کاملPredicting Binding Affinities of Fosmidomycin Analogues as Doxp-reductoisomerase Inhibitors Based on Structure-centric Approaches
Fosmidomycin and its derivatives belong to class DOX-reductoisomerase (DXR) inhibitors. A fosmidomycin analogues library was designed with 43 analogues, their molecular interactions and binding affinities with DXR (PDB ID: 1ONP) have been studied using Glide docking, QMpolarized ligand docking (QPLD), molecular mechanics based on generalized Born/surface area (MM-GB/SA) and multi-ligand bimolec...
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Isoprenoid biosynthesis via the methylerythritol phosphate pathway is a target against pathogenic bacteria and the malaria parasite Plasmodium falciparum. 4-(Hydroxyamino)-4-oxobutylphosphonic acid and 4-[hydroxy(methyl)amino]-4-oxobutyl phosphonic acid, two novel inhibitors of DXR (1-deoxy-D-xylulose 5-phosphate reducto-isomerase), the second enzyme of the pathway, have been synthesized and co...
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ژورنال
عنوان ژورنال: Journal of Medicinal Chemistry
سال: 2018
ISSN: 0022-2623,1520-4804
DOI: 10.1021/acs.jmedchem.8b01026