title: Synthesis and biological evaluation of analogs of AAL(S) for use as ceramide synthase 1 inhibitors.
abstract: A convergent synthesis to access hydrophobic tail analogs and head group modifications of AAL(S) is described. The analogs synthesised were evaluated for their ability to inhibit ceramide synthase 1 and for their cytotoxicity in K562 cells. Our results have identified inhibitors which are non-cytotoxic yet maintain CerS1 inhibition.
authors.affiliation: School of Chemistry, UNSW Australia, Sydney, NSW 2052, Australia. jonathan.morris@unsw.edu.au.
authors.forename: Hamish D
authors.initials: HD
authors.lastname: Toop
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Don
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Morris
mesh_terms: D000605:Amino Alcohols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000068876:Fingolimod Hydrochloride / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D020014:K562 Cells; D008954:Models, Biological; D015394:Molecular Structure; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*
chemical_list: C000611333:AAL(S) compound; D000605:Amino Alcohols; D004791:Enzyme Inhibitors; D010088:Oxidoreductases; C108138:dihydroceramide desaturase; D000068876:Fingolimod Hydrochloride