New PDMP analogues inhibit process outgrowth in an insect cell line

Jacob P Slavish; Donna K Friel; Lynne A Oland; Robin Polt

doi:10.1016/j.bmcl.2004.01.013

New PDMP analogues inhibit process outgrowth in an insect cell line

Bioorg Med Chem Lett. 2004 Mar 22;14(6):1487-90. doi: 10.1016/j.bmcl.2004.01.013.

Authors

Jacob P Slavish¹, Donna K Friel, Lynne A Oland, Robin Polt

Affiliation

¹ Department of Chemistry, University of Arizona, Tucson, AZ 85721, USA.

PMID: 15006387
DOI: 10.1016/j.bmcl.2004.01.013

Abstract

d-threo-1-Phenyl-2-aminodecanoyl-3-morpholinopropanol (d-threo-PDMP) has previously been shown to inhibit the biosynthesis of glycosphingolipids (GSLs) in mammals and mammalian cell lines by the inhibition of glucosylceramide synthase. New d-threo-PDMP analogues were synthesized from d-serine, and found to suppress neurite extension in an embryonic insect cell line from the moth Manduca sexta, and in explanted neural tissue from insect pupae. Inhibition occurred at lower concentrations than d-threo-PDMP. The observed suppression of neurite formation was found to be reversible after the removal of the compounds. Due to their small size and short life cycle, M. sexta is shown to be an ideal model organism for studies of GSL effects in cellular development, and for drug development studies.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Animals
Cell Division / drug effects
Cell Division / physiology
Cell Line
Growth Inhibitors / chemistry
Growth Inhibitors / pharmacology*
Manduca
Morpholines / chemistry
Morpholines / pharmacology*
Neurons, Afferent / cytology*
Neurons, Afferent / drug effects*

Substances

Growth Inhibitors
Morpholines
RV 538

Grants and funding

P01-NS28495/NS/NINDS NIH HHS/United States