title: Synthesis and biological evaluation of novel PDMP analogues.
abstract: A new series of hybrid PDMP analogues, based both on PDMP and styryl analogues of natural ceramide, has been synthesized from D-serine. The synthetic route was developed such that future introduction of different aryl groups is straightforward. Biological evaluation, both in vitro on rat liver Golgi fractions as well as in HEK-293 and COS-7 cells, revealed two lead compounds with comparable inhibitory potency as PDMP, which could be elaborated to more potent inhibitors.
authors.affiliation: Laboratory for Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Ghent University, Ghent 9000, Belgium.
authors.forename: Ulrik
authors.initials: U
authors.lastname: Hillaert
authors.forename: Swetlana
authors.initials: S
authors.lastname: Boldin-Adamsky
authors.forename: Jef
authors.initials: J
authors.lastname: Rozenski
authors.forename: Roger
authors.initials: R
authors.lastname: Busson
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Futerman
authors.forename: Serge
authors.initials: S
authors.lastname: Van Calenbergh
mesh_terms: D000818:Animals; D019556:COS Cells; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors*; D006056:Golgi Apparatus / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D015394:Molecular Structure; D009025:Morpholines / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D013347:Subcellular Fractions / Q000201:enzymology
chemical_list: D004791:Enzyme Inhibitors; D009025:Morpholines; C033110:RV 538; D005964:Glucosyltransferases; C023246:ceramide glucosyltransferase