No abstract

Anti-plasmodial activity-guided fractionation of Phlomis brunneogaleata (Lamiaceae) led to the isolation of two new metabolites, the iridoid glycoside, brunneogaleatoside and a new pyrrolidinium derivative (2S,4R)-2-carboxy-4-(E)-p-coumaroy- and X-ray crystallography. Compounds 10 and 11 were determined to be the major anti-malarial principles of the crude extract (IC 50 values of 2.4 and 5.9 mg/mL, respectively). They also exhibited significant leishmanicidal activity (IC 50 = 1.1 and 4.1 mg/mL, respectively). The inhibitory potential of the pure metabolites against plasmodial enoyl-ACP reductase (FabI), which is the key regulator of type II fatty acid synthases (FAS-II) in P. falciparum, was also assessed. Compound 10 showed promising FabI inhibiting effect (IC 50 = 10 mg/mL) and appears to be the first anti-malarial natural product targeting FabI of P. falciparum.

The qualitative and quantitative determination of phenylethanoid glycosides in methanolic extracts of five species of the genus Phlomis (Lamiaceae) has been investigated using a new reversed-phase HPLC method combined with photodiode-array detection and electrospray/MS analysis. Forsythoside B, verbascoside, samioside, alyssonoside, isoverbascoside, leucosceptosides A and B and martynoside were detected. The quantification of the above constituents was performed using echinacoside as internal standard. Knowledge of the content of phenylethanoid glycosides contributes to the chemotaxonomy of the genus.

Radical scavenger activities of 21 phenylethanoid glycosides, including 15 ester derivatives of caffeic, ferulic, vanillic and syringic acid as well as 6 deacyl derivatives were determined by quantifying their effects on the production of reactive oxygen species (ROS) in a luminol-enhanced chemiluminescence assay with formyl-methionyl-leucyl-phenylalanine (FMLP) stimulated human polymorphonuclear neutrophils (PMNs). All phenylethanoids acylated with phenolic acids showed strong antioxidant activity whereas the deacyl derivatives were more than 30-fold less active. Therefore, the antioxidant activity is mainly related to the number of aromatic methoxy and hydroxy groups and the structure of the acyl moiety (C6-C1 or C6-C3). In contrast, modification of the sugar chain or replacement of hydroxy groups by methoxy groups in the acyl or the phenylethanoid moiety is of minor importance. The position of the acyl moiety is without significance. Free caffeic, ferulic, vanillic and syringic acid are less active compared to the phenylethanoid derivatives. This points to the importance of dissociation and lipophilicity of these acids in a cellular test system.