title: The chemistry and biology of febrifugine and halofuginone.
abstract: The trans-2,3-disubstituted piperidine, quinazolinone-containing natural product febrifugine (also known as dichroine B) and its synthetic analogue, halofuginone, possess antimalarial activity. More recently studies have also shown that halofuginone acts as an agent capable of reducing fibrosis, an indication with clinical relevance for several disease states. This review summarizes historical isolation studies and the chemistry performed which culminated in the correct structural elucidation of naturally occurring febrifugine and its isomer isofebrifugine. It also includes the range of febrifugine analogues prepared for antimalarial evaluation, including halofuginone. Finally, a section detailing current opinion in the field of halofuginone's human biology is included.
authors.affiliation: Centre for Synthesis and Chemical Biology, School of Chemistry and Chemical Biology, University College Dublin, Dublin 4, Ireland.
authors.forename: Noel P
authors.initials: NP
authors.lastname: McLaughlin
authors.affiliation: Centre for Synthesis and Chemical Biology, School of Chemistry and Chemical Biology, University College Dublin, Dublin 4, Ireland. Electronic address: paul.evans@ucd.ie.
authors.forename: Paul
authors.initials: P
authors.lastname: Evans
authors.affiliation: Agricultural Research Organization, The Volcani Center, Institute of Animal Science, P.O. Box 6, Bet Dagan 50250, Israel. Electronic address: mark.pines@mail.huji.ac.il.
authors.forename: Mark
authors.initials: M
authors.lastname: Pines
mesh_terms: D000962:Antimalarials / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010880:Piperidines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010961:Plasmodium / Q000187:drug effects*; D011799:Quinazolines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D052999:Quinazolinones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D010880:Piperidines; D011799:Quinazolines; D052999:Quinazolinones; C001207:febrifugine; C010176:halofuginone
keywords: 3-Hydroxypiperidine; Antimalarial; Fibrosis; Isomerization; Natural product; Quinazolinone