Eleutherin

Application of MEKC and monolithic CEC for the analysis of bioactive naphthoquinones in Eleutherine americana.[Pubmed:19862752]

Electrophoresis. 2009 Nov;30(21):3757-63.

Two microscale separation techniques for the analysis of bioactive naphthoquinones in Eleutherine americana were developed and validated. By MEKC four compounds (eleuthoside B, isoEleutherin, eleutherol and Eleutherinoside A) could be determined in plant extracts using an aqueous electrolyte solution composed of 25 mM sodium tetraborate, 50 mM sodium cholate and 20% THF. CEC on a polymeric methacrylate-based monolith with strong cationic properties showed promising results, as it additionally enabled the separation of two enantiomers, Eleutherin and isoEleutherin. The mobile phase for CEC experiments comprised 3 mM ammonium formate in a mixture of ACN and water. At an applied voltage of -25 kV, all five markers were baseline separated in less than 12 min. Both methods were successfully validated for linearity (MEKC: R(2) > or = 0.999; CEC: R(2) > or = 0.997), sensitivity (MEKC: LOD = 4-5 microg/mL; CEC: LOD=2-8 microg/mL), accuracy (MEKC: 96.5-102.7% recovery; CEC: 97.1-103.5% recovery) and precision (MEKC: sigma(rel) < or = 2.43%; CEC: sigma(rel) < or = 2.21%). The quantitative analysis of naphthoquinone derivatives in several E. americana samples showed that both methods are suitable for practical applications, because the results were well comparable to those obtained by established techniques such as HPLC.

Effects of ethanolic extract and naphthoquinones obtained from the bulbs of Cipura paludosa on short-term and long-term memory: involvement of adenosine A(1) and A(2)A receptors.[Pubmed:23057724]

Basic Clin Pharmacol Toxicol. 2013 Apr;112(4):229-35.

Previous studies from our group have indicated important biological properties of the ethanolic extract and isolated compounds from the bulbs of Cipura paludosa (Iridaceae), a native plant widely distributed in northern Brazil, including antioxidant, neuroprotective and anti-nociceptive activities. In the present study, the effects of the ethanolic extract and its two naphthoquinones (Eleutherine and isoEleutherine) on the short- and long-term memory of adult rodents were assessed in social recognition and inhibitory avoidance tasks. Acute pre-training oral administration of the ethanolic extract improved the short-term social memory in rats as well as facilitated the step-down inhibitory avoidance short- and long-term memory in mice. Moreover, the co-administration of 'non-effective' doses of the extract of Cipura paludosa and the adenosine receptor antagonists caffeine (non-selective), DPCPX (adenosine A1 receptor antagonist) and ZM241385 (adenosine A2A receptor antagonist) improved the social recognition memory of rats. In the inhibitory avoidance task, the co-administration of sub-effective doses of the extract with caffeine or ZM241385, but not with DPCPX, improved the short- and long-term memory of mice. Finally, the acute oral administration of Eleutherine and isoEleutherine facilitated the inhibitory avoidance short- and long-term memory in mice. These results demonstrate for the first time the cognitive-enhancing properties of the extract and isolated compounds from the bulbs of Cipura paludosa in rodents and suggest a possible involvement of adenosine A1 and A2A receptors in these effects.

Antidermatophyte and antimelanogenesis compound from Eleutherine americana grown in Indonesia.[Pubmed:20155402]

J Nat Med. 2010 Apr;64(2):223-6.

An active compound from the bulb of Eleutherine americana L. Merr. (Iridaceae) collected from East Kalimantan, Indonesia, was tested for its antidermatophyte and antimelanogenesis activity. Antifungal assay-directed fractionation of the n-hexane-soluble fraction of the methanolic extract of the bulb of E. americana led to the isolation of 1 as an active compound. The compound was identified as the naphthoquinone Eleutherin by EI-MS and (1)H-, (13)C-, and two-dimensional NMR analyses. Antidermatophyte assay of 1 at concentrations of 10, 20, 40, 60, and 80 microg/disk and myconazole, a commercial antidermatophyte, at 10 microg/disk displayed 7, 8, 13, 16, 17, and 14 mm of inhibition zone against Trichophyton mentagrophytes, respectively. In a melanin formation inhibition assay, compound 1 displayed potent antimelanogenesis activity at 5 ppm with low toxicity compared with arbutin, a commercial skin-whitening agent. The results showed the high potential of 1, an active compound from E. americana, to be applied as an antidermatophyte and antimelanogenesis agent.

Antifungal Activity of Pyranonaphthoquinones Obtained from Cipura paludosa Bulbs.[Pubmed:26594766]

Nat Prod Commun. 2015 Sep;10(9):1589-92.

Previous studies with the bulbs of Cipura paludosa (Iridaceae) showed the presence of pyranonaphthoquinones, including Eleutherine, isoEleutherine and eleutherol. The aim of this study was to evaluate the antifungal properties of these compounds. The activity was tested against the clinically relevant yeasts Candida albicans, C. tropicalis, Saccharomyces cerevisiae and Cryptococcus neoformans with the microbroth dilution method, following the guidelines of CLSI. Eleutherine, isoEleutherine and eleutherol all presented significant antifungal activity, especially the first two, the major components, with MIC values between 7.8 and 250 microg/mL. In conclusion, these results demonstrate that C. paludosa bulbs produce active principles with relevant antifungal potential, contributing, at least in part, to the antimicrobial effect evidenced for this plant and justifying its popular use against infections.

A new naphthoquinone isolated from the bulbs of Cipura paludosa and pharmacological activity of two main constituents.[Pubmed:21283955]

Planta Med. 2011 Jul;77(10):1035-43.

Cipura paludosa (Iridaceae) is a plant that is distributed in the north region of Brazil. Its bulbs are used in folk medicine to treat inflammation and pain. Four naphthalene derivatives have been isolated from the bulbs of this plant. Three of them have been identified as the known naphthalene derivatives, Eleutherine, iso-Eleutherine, and hongkonin. The structure of the fourth and new component was determined as 11-hydroxyEleutherine by extensive NMR study. In addition, the IN VIVO effect of the two major compounds, Eleutherine and iso-Eleutherine, was evaluated in carrageenan-induced hypernociception and inflammation in mice. Eleutherine and iso-Eleutherine (1.04-34.92 micromol/kg), dosed intraperitoneally (i.p.) or orally (p.o.), decreased the carrageenan-induced paw oedema (i.p. - inhibitions of 36 +/- 7 % and 58 +/- 14 %, respectively; p.o. - inhibitions of 36 +/- 7 % and 58 +/- 14 %, respectively). Iso-Eleutherine, but not Eleutherine, significantly reduced (inhibitions of 39 +/- 4 %) the plasma extravasation induced by intradermal (i.d.) injection of carrageenan. Likewise, Eleutherine and iso-Eleutherine (1.04-34.92 micromol/kg, i.p. or p.o.) were also effective in preventing the carrageenan-induced hypernociceptive response (i.p. - inhibition of 59 +/- 4 % and 63 +/- 1 %, respectively; p.o. - inhibitions of 36 +/- 7 % and 58 +/- 14 %, respectively). It was also suggested that the anti-inflammatory and anti-hypernociceptive effects of Eleutherine or iso-Eleutherine partly depend on the interference with the synthesis or activity of mast cell products, kinins, cytokine, chemokines, prostanoids, or sympathetic amines. Our findings show that two major compounds of C. paludosa contain pharmacologically active constituents that possess antinociceptive and anti-inflammatory activity, justifying, at least in part, its popular therapeutic use for treating conditions associated with pain.

Synthesis and cytotoxicity of pyranonaphthoquinone natural product analogues under bioreductive conditions.[Pubmed:24436995]

Bioorg Med Chem. 2013 Dec 15;21(24):7971-80.

UNLABELLED: We have synthesised a focused library of derivatives of natural products containing the pyranonaphthoquinone moiety including the first report of such a scaffold with an appended tetrazole functionality. Examples include kalafungin derivatives as well as analogues of nanaomycin and Eleutherin. These compounds were assessed for cytotoxic activation by breast cancer cell lines engineered to express the prototypic human one- and two-electron quinone bioreductive enzymes, NADPH: cytochrome P450 oxidoreductase (POR) and NAD(P)H: quinoneoxidoreductase 1 (NQO1; DT-diaphorase), respectively. Several compounds were observed to be cytotoxic at sub-micromolar level and a pattern of increased aerobic potency was observed in cells over expressing POR. A subset of analogues was assessed under anoxic conditions, where cytotoxicity was reduced, implicating redox cycling as a major mechanism of toxicity. The substrate specificity for reductive enzymes is relevant to the future design of bioreductive prodrugs to treat cancer.

Polyketides from Eleutherine bulbosa.[Pubmed:20835959]

Nat Prod Res. 2010 Oct;24(16):1578-86.

Four new polyketides, (R)-4-hydroxyEleutherin, eleuthone, Eleutherinol-8-O-beta-D-glucoside and isoeleuthoside C (dihydroisoEleutherin-5-O-beta-D-gentiobioside) were isolated from the bulbs of Eleutherine bulbosa, to join Eleutherin, isoEleutherin, Eleutherinol, eleutherol, eleuthoside B (eleutherol-4-O-beta-D-gentiobioside), eleuthoside C (dihydroEleutherin-5-O-beta-D-gentiobioside), hongconin (4-oxodihydroisoEleutherin) and elecanacin, which have already been isolated from the same plant. The structures of the new polyketides, based on oxydated cyclic systems, have been elucidated by chemical and spectroscopic methods.