Cytotoxic constituents and a new hydroxycinnamic acid derivative from Leontodon saxatilis (Asteraceae, Cichorieae).

In our ongoing research for the discovery of new constituents with antimyeloma activity, we investigated 15 compounds present in the aerial parts of Leontodon saxatilis for their cytotoxic potential against NCI-H929, U266, and OPM2 cell lines. One of the isolated compounds displayed a new natural product and was identified as 5-feruloyl-2α-hydroxyquinic acid after LC-MS and NMR experiments. Of the remaining compounds, cichoric acid and three flavone glycosides, apigenin 4'-O-ß-d-glucoside, luteolin 7-O-ß-d-glucoside and luteolin 4'-O-ß-d-glucoside, showed moderate cytotoxic activity, whereas the effects of two aglyones apigenin and luteolin were more pronounced. Though the cytotoxic potential of the two aglycones (against other cell lines) was reported in various studies, our work moreover showed that cooccurrence of these two compounds with similar components of lower activity led to comparable results and at the same time minimized the damage of healthy fibroblast cells. Thus, our work could be a starting point for additional studies on the synergistic effect of similar components against myeloma cell lines.

7-Isopentenyloxycoumarin: What Is New across the Last Decade.

7-Isopentenyloxycoumarin is among the most widespread naturally occurring prenyloxy umbelliferone derivatives. This secondary metabolite of mixed biosynthetic origin has been typically isolated from plants belonging to several genera of the Rutaceae and Apiaceae families, comprising widely used medicinal plants and in general plants with beneficial effects on human welfare, as well as edible fruits and vegetables. Although known for quite a long time (more than 50 years), only in the last two decades has this natural compound been revealed to exert powerful and promising pharmacological properties, such as active cancer chemopreventive, antibacterial, antiprotozoal, antifungal, anti-inflammatory, neuroprotective, and antioxidant properties, among the activities best outlined in the recent literature. The aim of this comprehensive miniature review article is to detail the novel natural sources and the effects described during the last decade for 7-isopentenyloxycoumarin and what has been reported on the mechanisms of action underlying the observed biological activities of this oxyprenylated secondary metabolite. In view of the herein described data, suggestions on how to address future research on the abovementioned natural product and structurally related derivatives in the best ways according to the authors will be also provided.

Gercumin synergizes the action of 5-fluorouracil and oxaliplatin against chemoresistant human cancer colon cells.

Advanced colon cancer is extremely difficult to cure, underscoring the need to develop novel therapeutic agents. Prenylated curcumins that are semisynthetic curcumin derivatives with significant anti-cancer potential have been studied herein to assess their therapeutic potential for colon cancer and tested to this aim in vitro for their growth inhibitory properties against 5-fluorouracil + oxaliplatin resistant human colon cancer CR-HT29 and HCT-116 cells. The resulting most active product, gercumin (mono-O-geranylcurcumin), has been further tested for its synergistic effects with FOLFOX (a combination of 5-fluorouracil and oxaliplatin) on the same cell lines. Activity of this combination on colonosphere formation was also investigated. Gercumin was able to suppress the growth of cancer cells with a potency similar to that of curcumin. A synergistic effect of this compound and FOLFOX was also observed. doses tested for synergy in the colonosphere assays did not show greater suppression of colonosphere formation than independent treatment with either reagent alone. Only one of the combinations was shown to be more effective at suppressing colonosphere formation [gercumin 5  µM + FOLFOX (2x)]. Thus, the growth inhibitory effects of curcumin against human cancer cells can be modulated and enhanced by the introduction of hydrophobic chains, normally found in several natural compounds, like the geranyl one. Such compounds are also able to synergize with known chemotherapeutics.

Biomolecular Targets of Oxyprenylated Phenylpropanoids and Polyketides.

Oxyprenylated secondary metabolites (e.g. phenylpropanoids and polyketides) represent a rare class of natural compounds. Over the past two decades, this group of phytochemicals has become a topic of intense research activity by several teams worldwide due to their in vitro and in vivo pharmacological activities, and to their great therapeutic and nutraceutical potential for the chemoprevention of acute and chronic diseases affecting humans. Such investigations have provided evidence that oxyprenylated secondary metabolites are able to interact with several biological targets at different levels accounting for their observed anticarcinogenic, anti-inflammatory, neuroprotective, immunomodulatory, antihypertensive, and metabolic effects. The aim of the present contribution is to provide a detailed survey of the so far reported data on the capacities of selected oxyprenylated phenylpropanoids and polyketides to trigger receptors, enzymes, and other types of cellular factors for which they exhibit a high degree of affinity and therefore evoke specific responses. With respect to the rather small amounts of these compounds available from natural sources, their chemical synthesis is also highlighted.

Novel biologically active principles from spinach, goji and quinoa.

Spinach leaves, goji berries and quinoa seeds are claimed to have a great nutraceutical potential due to their high content of compounds providing benefits for human health, such as amino acids, polyunsaturated fatty acids, carotenoids, betaine, vitamins, fibre, minerals and polyphenols. Samples of these plants were extracted with different solvent mixtures (e.g. EtOH, H2O/EtOH 3:7 and H2O/EtOH 7:3) and extractions were accomplished using a microwave apparatus. Subsequent UHPLC analysis and photodiode array detection were employed for the quantification of biologically active compounds like 7-isopentenyloxycoumarin, auraptene, umbelliprenin, boropinic acid and 4'-geranyloxyferulic acid. EtOH was found to be the best solvent in terms of extractive yields and the above-mentioned phytochemicals were recorded in the concentration range 2.01-49.22 µg/g dry extract. The findings depicted herein revealed that spinach, goji and quinoa are good sources of oxyprenylated umbelliferone and ferulic acid derivatives.

Selenylated plant polysaccharides: A survey of their chemical and pharmacological properties.

Polysaccharides from plants and fungi are considered nowadays as powerful pharmacological tools with a great therapeutic potential. In the meantime, efforts have been addressed to set up effective chemical modifications of naturally occurring polysaccharides to improve their biological effects as well as to positively modify some key parameters like solubility, bioavailability, pharmacokinetic, and similar. To this concern much attention has been focused during the last decade to the selenylation of natural polysaccharides from plants, algae, and fungi, the use of which is already encoded in ethnomedical traditions. The aim of this review article is to provide a detailed survey of the in so far reported literature data and a deeper knowledge about the state of the art on the chemical and pharmacological properties of selenylated polysaccharides of plant, algal, and fungal origin in terms of anti-oxidant, anti-cancer, anti-diabetic, and immunomodulatory activities. In all cases, literature data revealed that selenylation greatly improved such properties respect to the parent polysaccharides, indicating that selenylation is a valid, alternative, and effective chemical modification of naturally occurring carbohydrates.

Natural oxyprenylated coumarins are modulators of melanogenesis.

Naturally occurring coumarins 7-isopentenyloxycoumarin, auraptene, and umbelliprenin are able to modulate the biosynthesis of melanin in murine Melan-a cells probably through the interaction with selected biological targets like estrogen receptor ß and aryl hydrocarbon receptor. Such a modulation strictly depends on the individual structure of the coumarin: the presence of a 3,3-dimethylallyloxy side chain is a structural determinant for tanning activation whereas a farnesyl one leads to the opposite effect. The parent compound with a free OH group, umbelliferone, did not provide any interaction. Other coumarins assayed, having shorter chains and/or being substituted in other positions, and prenyloxypsoralens, were not active or not further investigated in this context being cytotoxic at low doses.

Analysis of biologically active oxyprenylated phenylpropanoids in Tea tree oil using selective solid-phase extraction with UHPLC-PDA detection.

An efficient analytical strategy based on different extraction methods of biologically active naturally occurring oxyprenylated umbelliferone and ferulic acid derivatives 7-isopentenyloxycoumarin, auraptene, umbelliprenin, boropinic acid, and 4'-geranyloxyferulic acid and quantification by UHPLC with spectrophotometric (UV/Vis) detection from Tea tree oil is reported. Absorption of the pure oil on Al2O3 (Brockmann activity II) prior washing the resulting solid with MeOH and treatment of this latter with CH2Cl2 resulted the best extraction methodology in terms of yields of oxyprenylated secondary metabolites. Among the five O-prenylphenylpropanoids herein under investigation auraptene and umbelliprenin were never detected while 4'-geranyloxyferulic acid was the most abundant compound resulting from all the three extraction methods employed. The UHPLC analytical methodology set up in the present study resulted to be an effective and versatile technique for the simultaneous characterization and quantification of prenyloxyphenylpropanoids in Tea tree oil and applicable to other complex matrices from the plant kingdom.

A green deep eutectic solvent dispersive liquid-liquid micro-extraction (DES-DLLME) for the UHPLC-PDA determination of oxyprenylated phenylpropanoids in olive, soy, peanuts, corn, and sunflower oil.

A green dispersive liquid-liquid microextraction (DLLME) using deep eutectic solvent (DES) as the extracting solvent has been developed and applied for the simultaneous quantification of ferulic acid, umbelliferone, boropinic acid, 7-isopentenyloxycoumarin, 4'-geranyloxyferulic acid (GOFA), and auraptene in some vegetable oils using ultra high performance liquid chromatography (UHPLC) with photodiode array detection (PDA). All parameters in the extraction step, including selection and loading of both extracting and dispersing solvents, amount of both extractant and disperser solvent were investigated and optimized. PhAA/TMG DES achieved higher recovery and enrichment factor compared to other DESs. The validated method showed good linearity with correlation coefficients, r2>0.9990 for all the analytes. Furthermore, this is the first time that eco-friendly solvents are used for the extraction of oxyprenylated phenylpropanoids and the corresponding extract analyzed with ultra high performance liquid chromatography with photodiode array detection.