A New Alkamide with an Endoperoxide Structure from Acmella ciliata (Asteraceae) and Its in Vitro Antiplasmodial Activity.
From the aerial parts of Acmella ciliata (H.B.K.) Cassini (basionym Spilanthes ciliata Kunth; Asteraceae), three alkamides were isolated and identified by mass- and NMR spectroscopic methods as (2E,6E,8E)-N-isobutyl-2,6,8-decatrienamide (spilanthol, (1)), N-(2-phenethyl)-2E-en-6,8-nonadiynamide (2) and (2E,7Z)-6,9-endoperoxy-N-isobutyl-2,7-decadienamide (3). While 1 and 2 are known alkamides, compound 3 has not been described until now. It was found that the unusual cyclic peroxide 3 exists as a racemate of both enantiomers of each alkamide; the 6,9-cis- as well as the 6,9-trans-configured diastereomers, the former represents the major, the latter the minor constituent of the mixture. In vitro tests for activity against the human pathogenic parasites Trypanosoma brucei rhodesiense and Plasmodium falciparum revealed that 1 and 3 possess activity against the NF54 strain of the latter (IC50 values of 4.5 and 5.1 µM, respectively) while 2 was almost inactive. Compound 3 was also tested against multiresistant P. falciparum K1 and was found to be even more active against this parasite strain (IC50 = 2.1 µM) with considerable selectivity (IC50 against L6 rat skeletal myoblasts = 168 µM).
Departamento de Ci&#234;ncias Farmac&#234;uticas, Centro de Ci&#234;ncias da Sa&#250;de, Bloco J/K, Universidade Federal de Santa Catarina, Florian&#243;polis 88040-900, SC, Brazil. silveira.narjara@gmail.com.
Narjara
N
Silveira
Departamento de Ci&#234;ncias Farmac&#234;uticas, Centro de Ci&#234;ncias da Sa&#250;de, Bloco J/K, Universidade Federal de Santa Catarina, Florian&#243;polis 88040-900, SC, Brazil. jsaar@hotmail.de.|Institut f&#252;r Pharmazeutische Biologie und Phytochemie (IPBP), University of M&#252;nster, PharmaCampus, Corrensstraße 48, M&#252;nster D-48149, Germany. jsaar@hotmail.de.
Julia
J
Saar
Departamento de Qu&#237;mica, Universidade Federal do Paran&#225;, Curitiba 81530-900, PR, Brazil. alandiego@ufpr.br.
Alan Diego C
AD
Santos
Departamento de Qu&#237;mica, Universidade Federal do Paran&#225;, Curitiba 81530-900, PR, Brazil. anderbarison@gmail.com.
Andersson
A
Barison
Departamento de Ci&#234;ncias Farmac&#234;uticas, Centro de Ci&#234;ncias da Sa&#250;de, Bloco J/K, Universidade Federal de Santa Catarina, Florian&#243;polis 88040-900, SC, Brazil. p.l.sandjo@ufsc.br.
Louis P
LP
Sandjo
Swiss Tropical and Public Health Institute (Swiss TPH), Socinstr. 57, Basel CH-4051, Switzerland. marcel.kaiser@unibas.ch.|University of Basel, Petersplatz 1, Basel CH-4003, Switzerland. marcel.kaiser@unibas.ch.
Marcel
M
Kaiser
Institut f&#252;r Pharmazeutische Biologie und Phytochemie (IPBP), University of M&#252;nster, PharmaCampus, Corrensstraße 48, M&#252;nster D-48149, Germany. thomschm@uni-muenster.de.
Thomas J
TJ
Schmidt
Departamento de Ci&#234;ncias Farmac&#234;uticas, Centro de Ci&#234;ncias da Sa&#250;de, Bloco J/K, Universidade Federal de Santa Catarina, Florian&#243;polis 88040-900, SC, Brazil. maique.biavatti@ufsc.br.
Maique W
MW
Biavatti
D000818:Animals; D019659:Asteraceae / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000472:pathogenicity; D053284:Polyunsaturated Alkamides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D051381:Rats; D013237:Stereoisomerism; D014346:Trypanosoma brucei brucei / Q000187:drug effects / Q000472:pathogenicity
D053284:Polyunsaturated Alkamides
Acmella ciliata; Asteraceae; Plasmodium falciparum; alkamide; antiplasmodial activity; endoperoxide; jambu