title: Aurapten, a coumarin with growth inhibition against Leishmania major promastigotes.
abstract: Several natural compounds have been identified for the treatment of leishmaniasis. Among them are some alkaloids, chalcones, lactones, tetralones, and saponins. The new compound reported here, 7-geranyloxycoumarin, called aurapten, belongs to the chemical class of the coumarins and has a molecular weight of 298.37. The compound was extracted from the Rutaceae species Esenbeckia febrifuga and was purified from a hexane extract starting from 407.7 g of dried leaves and followed by four silica gel chromatographic fractionation steps using different solvents as the mobile phase. The resulting compound (47 mg) of shows significant growth inhibition with an LD50 of 30 microM against the tropical parasite Leishmania major, which causes severe clinical manifestations in humans and is endemic in the tropical and subtropical regions. In the present study, we investigated the atomic structure of aurapten in order to determine the existence of common structural motifs that might be related to other coumarins and potentially to other identified inhibitors of Leishmania growth and viability. This compound has a comparable inhibitory activity of other isolated molecules. The aurapten is a planar molecule constituted of an aromatic system with electron delocalization. A hydrophobic side chain consisting of ten carbon atoms with two double bonds and negative density has been identified and may be relevant for further compound synthesis.
authors.affiliation: Laboratório de Proteína, Cristalografia e Biologia Estructural, Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos, SP, Brazil.
authors.forename: H B
authors.initials: HB
authors.lastname: Napolitano
authors.forename: M
authors.initials: M
authors.lastname: Silva
authors.forename: J
authors.initials: J
authors.lastname: Ellena
authors.forename: B D G
authors.initials: BD
authors.lastname: Rodrigues
authors.forename: A L C
authors.initials: AL
authors.lastname: Almeida
authors.forename: P C
authors.initials: PC
authors.lastname: Vieira
authors.forename: G
authors.initials: G
authors.lastname: Oliva
authors.forename: O H
authors.initials: OH
authors.lastname: Thiemann
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D003374:Coumarins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D007896:Leishmaniasis / Q000188:drug therapy*; D021261:Parasitic Sensitivity Tests; D010936:Plant Extracts / Q000494:pharmacology; D027821:Rutaceae
chemical_list: D000981:Antiprotozoal Agents; D003374:Coumarins; D010936:Plant Extracts; C105832:aurapten