Anders Karlén

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Mycobacterium tuberculosis glutamine synthetase (MtGS) is a promising target for antituberculosis drug discovery. In a recent high-throughput screening study we identified several classes of MtGS inhibitors targeting the ATP-binding site. We now explore one of these classes, the 2-tert-butyl-4,5-diarylimidazoles, and present the design, synthesis, and X-ray(More)
Antibiotics are the medical wonder of our age, but an increasing frequency of resistance among key pathogens is rendering them less effective. If this trend continues the consequences for cancer patients, organ transplant patients, and indeed the general community could be disastrous. The problem is complex, involving abuse and overuse of antibiotics(More)
This study describes the use of alignment-independent descriptors for obtaining qualitative and quantitative predictions of the competitive inhibition of CYP2C9 on a serie of highly structurally diverse compounds. This was accomplished by calculating alignment independent descriptors in ALMOND. These GRid INdependent Descriptors (GRIND) represent the most(More)
A total of 945 known actives and roughly 10 000 decoy compounds were docked to eight different targets, and the resulting poses were scored using 10 different scoring functions. Three different score postprocessing methods were evaluated with respect to improvement of the enrichment in virtual screening. The three procedures were (i) multiple active site(More)
Virtual screening is widely applied in drug discovery, and significant effort has been put into improving current methods. In this study, we have evaluated the performance of compound ranking in virtual screening using five different data fusion algorithms on a total of 16 data sets. The data were generated by docking, pharmacophore search, shape(More)
Glutamine synthetase (GS, EC; also known as gamma-glutamyl:ammonia ligase) catalyzes the ATP-dependent condensation of glutamate and ammonia to form glutamine. The enzyme has essential roles in different tissues and species, which have led to its consideration as a drug or an herbicide target. In this article, we describe studies aimed at the(More)
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(More)
The possibility of improving the predictive ability of comparative molecular field analysis (CoMFA) by settings optimization has been evaluated to show that CoMFA predictive ability can be improved. Ten different CoMFA settings are evaluated, producing a total of 6120 models. This method has been applied to nine different data sets, including the widely(More)
Cinnamaldehyde derivatives were synthesized in good to excellent yields in one step by a mild and selective, base-free palladium(II)-catalyzed oxidative Heck reaction starting from acrolein and various arylboronic acids. Prepared α,β-unsaturated aldehydes were used for synthesis of novel α-aryl substituted fosmidomycin analogues, which were evaluated for(More)