Silveira Narjara, Saar Julia, Santos Alan Diego C, Barison Andersson, Sandjo Louis P, Kaiser Marcel, Schmidt Thomas J, Biavatti Maique W
Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Bloco J/K, Universidade Federal de Santa Catarina, Florianópolis 88040-900, SC, Brazil.
Institut für Pharmazeutische Biologie und Phytochemie (IPBP), University of Münster, PharmaCampus, Corrensstraße 48, Münster D-48149, Germany.
Molecules. 2016 Jun 11;21(6):765. doi: 10.3390/molecules21060765.
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).
从睫毛金钮扣（Acmella ciliata (H.B.K.) Cassini，异名：刺毛金钮扣Spilanthes ciliata Kunth；菊科）的地上部分分离得到了三种链状酰胺，通过质谱和核磁共振光谱法鉴定为(2E,6E,8E)-N-异丁基-2,6,8-癸三烯酰胺（尖叶番荔枝酰胺，(1)）、N-(2-苯乙基)-2E-烯-6,8-壬二炔酰胺(2)以及(2E,7Z)-6,9-内过氧基-N-异丁基-2,7-癸二烯酰胺(3)。虽然1和2是已知的链状酰胺，但化合物3此前尚未见报道。发现这种不寻常的环状过氧化物3以两种对映体的外消旋体形式存在，即6,9-顺式和6,9-反式构型的非对映异构体，前者是混合物中的主要成分，后者是次要成分。针对人类致病寄生虫布氏罗得西亚锥虫和恶性疟原虫的体外活性测试表明，1和3对后者的NF54菌株具有活性（IC50值分别为4.5和5.1 μM），而2几乎没有活性。化合物3还针对多重耐药的恶性疟原虫K1进行了测试，发现其对该寄生虫菌株的活性更高（IC50 = 2.1 μM），且具有相当高的选择性（对L6大鼠骨骼肌成肌细胞的IC50 = 168 μM）。
