Synthesis and biological evaluation of novel PDMP analogues.
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.
Hillaert
Ulrik
U
Laboratory for Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Ghent University, Ghent 9000, Belgium.
Boldin-Adamsky
Swetlana
S
Rozenski
Jef
J
Busson
Roger
R
Futerman
Anthony H
AH
Van Calenbergh
Serge
S
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
D004791:Enzyme Inhibitors; D009025:Morpholines; C033110:RV 538; D005964:Glucosyltransferases; C023246:ceramide glucosyltransferase