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 compund 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 LD 50 of 30 µM 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.

Synthesis, Leishmanicidal and Cytotoxic Activity of Triclosan-Chalcone, Triclosan-Chromone and Triclosan-Coumarin Hybrids

“…(16 (19). Yield 75% (0.204 mmol, 117 mg); yellow pale oil; IR (cm (25). Yield 79% (0.279 mmol, 137 mg); yellow pale oil; IR ( (27).…”

“…Aurapten, a 7-geranyloxycoumarin, was extracted from the Rutaceae species Esenbeckia febrifuga. This compound shows significant growth inhibition with a 50% inhibitory concentration (IC 50 ) of 30 µM against L. major [25]. Three coumarins isolated from the leaves of Galipea panamensis were tested against axenic amastigote forms of L. panamensis and displayed 50% effective concentrations (EC 50 ) of 9.9, 10.5, and 14.1 µg/mL, respectively [26].…”

Quinoline alkaloids and friedelane-type triterpenes isolated from leaves and wood of Esenbeckia alata kunt (Rutaceae)

“…6 In addition, a geranylcoumarin has been isolated from E. febrifuga, which significantly inhibited the growth of tropical parasite Leishmania major. 7 Phytochemical studies on this genus has allowed the isolation of several secondary metabolites such as flavonoids from E. yaxhoob, 4 E. grandiflora subsp. brevipetiolata, E. almawillia, and E. berlandieri ssp.…”

Alcaloides β-indolopiridoquinazolínicos de Esenbeckia grandiflora mart. (Rutaceae)

“…1 Destas, 22 espécies, incluindo E. grandiflora, tiveram sua constituição química investigada. Dentre os compostos isolados, alcaloides furoquinolínicos (E. alata, 3 E. almawillia, 2,4 E. berlandieri, 5 E. belizencis, 6 E. conspecta, 7 E. flava, 5 E. febrifuga, 8 E. hieronimi, 9 E. leiocarpa, 10 E. litoralis, 5,11 E. pentaphylla, 12 E. pilocarpoides 13 e E. yaxhoob 14 ), quinolinônicos (E. almawillia, 2,4,[15][16][17] E. belizencis, 6 E. flava, 5 E. hieronimi 9 e E. leiocarpa, 10,18,19 E. pentaphylla 12 e E. pilocarpoides 13 ) e acridônicos (E. litoralis, 5 E. pentaphylla, 12 E. pilocarpoides 13 ), derivados alquil-, pirano-e furocumarínicos (E. alata, 3,20 E. almawillia, 4 E. berlandieri, 5 E. conspecta, 7 E. flava, 5 E. febrifuga, 21 E. hieronimi, 9 E. leiocarpa, 10 E. litoralis, 5,11 E. ovata, 22 E. pentaphylla 12 e E. yaxhoob 23 ) e os limonoides (E. berlandieri, 5 E. flava, 5 E. febrifuga, 24 E. litoralis, 5 E. hartmanni, …”