Simple jQuery Dropdowns
Please use this identifier to cite or link to this item:
Full metadata record
DC FieldValueLanguage
dc.contributor.authorGeoffrey Schwertzen_US
dc.contributor.authorMichelle S. Freien_US
dc.contributor.authorMatthias C. Witschelen_US
dc.contributor.authorMatthias Rottmannen_US
dc.contributor.authorUbolsree Leartsakulpanichen_US
dc.contributor.authorPenchit Chitnumsuben_US
dc.contributor.authorAritsara Jaruwaten_US
dc.contributor.authorWanwipa Ittaraten_US
dc.contributor.authorAnja Schäferen_US
dc.contributor.authorRaphael A. Aponteen_US
dc.contributor.authorNils Trappen_US
dc.contributor.authorKerstin Marken_US
dc.contributor.authorPimchai Chaiyenen_US
dc.contributor.authorFrançois Diederichen_US
dc.contributor.otherETH Zurichen_US
dc.contributor.otherBASF SEen_US
dc.contributor.otherSwiss Tropical and Public Health Institute (Swiss TPH)en_US
dc.contributor.otherUniversitat Baselen_US
dc.contributor.otherThailand National Center for Genetic Engineering and Biotechnologyen_US
dc.contributor.otherMahidol Universityen_US
dc.contributor.otherVidyasirimedhi Institute of Science and Technologyen_US
dc.identifier.citationChemistry - A European Journal. Vol.23, No.57 (2017), 14345-14357en_US
dc.description.abstract© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Malaria remains a major threat to mankind due to the perpetual emergence of resistance against marketed drugs. Twenty-one pyrazolopyran-based inhibitors bearing terminal biphenyl, aryl sulfonamide, or aryl sulfone motifs were synthesized and tested towards serine hydroxymethyltransferase (SHMT), a key enzyme of the folate cycle. The best ligands inhibited Plasmodium falciparum (Pf) and Arabidopsis thaliana (At) SHMT in target, as well as PfNF54 strains in cell-based assays in the low nanomolar range (18–56 nm). Seven co-crystal structures with P. vivax (Pv) SHMT were solved at 2.2–2.6 Å resolution. We observed an unprecedented influence of the torsion angle of ortho-substituted biphenyl moieties on cell-based efficacy. The peculiar lipophilic character of the sulfonyl moiety was highlighted in the complexes with aryl sulfonamide analogues, which bind in their preferred staggered orientation. The results are discussed within the context of conformational preferences in the ligands.en_US
dc.rightsMahidol Universityen_US
dc.titleConformational Aspects in the Design of Inhibitors for Serine Hydroxymethyltransferase (SHMT): Biphenyl, Aryl Sulfonamide, and Aryl Sulfone Motifsen_US
Appears in Collections:Scopus 2016-2017

Files in This Item:
There are no files associated with this item.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.