Gerardiins A-L and Structurally Related Phenanthrenes from the Halophyte Plant Juncus gerardii and Their Cytotoxicity against Triple-Negative Breast Cancer Cells.

Species in the Juncaceae accumulate different types of secondary metabolites, among them phenanthrenes and 9,10-dihydrophenanthrenes in substantial amounts. These compounds have chemotaxonomic significance and also possess interesting pharmacological activities. The present study has focused on the isolation, structure determination, and pharmacological investigation of phenanthrenes from Juncus gerardii. Twenty-six compounds, including 23 phenanthrenes, have been isolated from a methanol extract of this plant. Twelve compounds, the phenanthrenes gerardiins A-L (1-12), were obtained as new natural products. Eleven phenanthrenes [effusol (13), dehydroeffusol (14), effususin A (15), compressin A, 7-hydroxy-2-methoxy-1-methyl-5-vinyl-9,10-dihydrophenanthrene, juncusol, 2-hydroxy-7-hydroxymethyl-1-methyl-5-vinyl-9,10-dihydrophenanthrene, 2,7-dihydroxy-5-formyl-1-methyl-9,10-dihydrophenanthrene, effususol A, 2,7-dihydroxy-5-hydroxymethyl-1-methyl-9,10-dihydrophenanthrene, and jinflexin C], 1-O-p-coumaroyl-3-O-feruloyl-glycerol, and the flavones apigenin and luteolin were isolated for the first time from this plant. The cytotoxicity of the 23 isolated phenanthrenes in both mouse (4T1) and human (MDA-MB-231) triple-negative breast cancer cells and in a nontumor (D3, human cerebral microvascular endothelial) cell line was tested using an MTT viability assay. The results obtained showed that the dimeric compounds gerardiins I (9), J (10), K (11), and L (12), derived biogenetically from effusol and dehydroeffusol, were cytotoxic to both tumor and nontumor cell lines, while the monomeric compounds exerted no or very low cytotoxicity. Impedance measurements were consistent with the results of the MTT assays performed.

Flavonoid, stilbene and diarylheptanoid constituents of Persicaria maculosa Gray and cytotoxic activity of the isolated compounds.

Persicaria maculosa (Polygonaceae) has been used as edible and as medicinal plant since ancient times. As a result of multistep chromatographic purifications, chalcones [2'-hydroxy-3',4',6'-trimethoxychalcone (1), pashanone (2), pinostrobin chalcone (3)], flavanones [6-hydroxy-5,7-dimethoxyflavanone (4), pinostrobin (5), onysilin (6), 5-hydroxy-7,8-dimethoxyflavanone (7)], flavonol [3-O-methylgalangin (8)], stilbene [persilben (9)], diarylheptanoids [1,7-diphenylhept-4-en-3-one (10), dihydroyashabushiketol (12), yashabushidiol B (13)] and 3-oxo-α-ionol-glucoside (11) were isolated from P. maculosa. The present paper reports for the first time the occurrence of diarylheptanoid-type constituents in the family Polygonaceae. Cytotoxicity of 1-5, 7 and 9-11 on 4 T1 mouse triple negative breast cancer cells was assayed by MTT test. None of the tested compounds reduced the cell viability to less than 80% of the control. On non-tumorigenic D3 human brain endothelial cells the decrease of cell viability was observed in case of 1 and 2. Further impedance measurements on 4 T1 and D3 cells a concentration-dependent decrease in the cell index of both cell types was demonstrated for 1, while 2 proved to be toxic only on endothelial cells.

Quinidine as an ABCB1 probe for testing drug interactions at the blood-brain barrier: an in vitro in vivo correlation study.

This study provides evidence that quinidine can be used as a probe substrate for ABCB1 in multiple experimental systems both in vitro and in vivo relevant to the blood-brain barrier (BBB). The combination of quinidine and PSC-833 (valspodar) is an effective tool to assess investigational drugs for interactions on ABCB1. Effects of quinidine and substrate-inhibitor interactions were tested in a membrane assay and in monolayer assays. The authors compared quinidine and digoxin as ABCB1 probes in the in vitro assays and found that quinidine was more potent and at least as specific as digoxin in ATPase and monolayer efflux assays employing MDCKII-MDR1 and the rat brain microcapillary endothelial cell system. Brain exposure to quinidine was tested in dual-/triple-probe microdialysis experiments in rats by assessing levels of quinidine in blood and brain. Comparing quinidine levels in dialysate samples from valspodar-treated and control animals, it is evident that systemic/local administration of the inhibitor diminishes the pumping function of ABCB1 at the BBB, resulting in an increased brain penetration of quinidine. In sum, quinidine is a good probe to study ABCB1 function at the BBB. Moreover, quinidine/PSC-833 is an ABCB1-specific substrate/inhibitor combination applicable to many assay systems both in vitro and in vivo.