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Bufadienolides are structurally related to the clinically relevant cardenolides (e.g., digoxin) and are now considered as endogenous steroid hormones. Binding of ouabain to Na(+)-K(+)-ATPase has been associated, in kidney cells, to the activation of the Src kinase pathway and Na(+)-K(+)-ATPase internalization. Nevertheless, whether the activation of this cascade also occurs with other cardiotonic steroids and leads to diuresis and natriuresis in the isolated intact kidney is still unknown. In the present work, we perfused rat kidneys for 120 min with bufalin (1, 3, or 10 μM) and measured its vascular and tubular effects. Thereafter, we probed the effect of 10 μM 3-(4-chlorophenyl)1-(1,1-dimethylethyl)-1H-pyrazolo[3,4-d]pyrimidin-4amine (PP2), a Src family kinase inhibitor, and 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio] butadiene (UO126), a highly selective inhibitor of both MEK1 and MEK2, on bufalin-induced renal alterations. Bufalin at 3 and 10 μM profoundly increased several parameters of renal function in a time- and/or concentration-dependent fashion. At a concentration that produced similar inhibition of the rat kidney Na(+)-K(+)-ATPase, ouabain had a much smaller diuretic and natriuretic effect. Although bufalin fully inhibited the rat kidney Na(+)-K(+)-ATPase in vitro, its IC(50) (33 ± 1 μM) was threefold higher than the concentration used ex vivo and all its renal effects were blunted by PP2 and UO126. Furthermore, the phosphorylated (activated) ERK1/2 expression was increased after bufalin perfusion and this effect was totally prevented after PP2 pretreatment. The present study shows for the first time the direct diuretic, natriuretic, and kaliuretic effects of bufalin in isolated rat kidney and the relevance of Na(+)-K(+)-ATPase-mediated signal transduction.

Os extratos orgânicos das folhas e raízes de Psychotria stachyoides forneceram o novo alcaloide indólico monoterpênico glicosilado N-desmetil-correantosida, além de bizantionosida B, a-amirina, éter metílico da alizarina, rubiadina, escopoletina, ácido barbinévico e uma mistura de b-sitosterol e estigmasterol glicosilados. A caracterização estrutural dos compostos isolados foi estabelecida com base na espectroscopia no infravermelho (IR), espectrometria de massa (MS) e particularmente ressonância magnética nuclear (RMN) 1D e 2D.The organic extracts of leaves and roots of Psychotria stachyoides provided the new glucoside monoterpenoid indole alkaloid N-demethylcorreantoside, besides bizantionoside B, a-amyrin, alizarine methyl-ether, rubiadine, scopoletin, barbinevic acid and a mixture of b-sitosterol and stigmasterol glucosides. The structural characterization of the isolates was established based on infrared spectroscopy (IR), mass spectrometry (MS) and, particularly, 1D and 2D nuclear magnetic resonance (NMR). Keywords: monoterpene indole alkaloid, coumarins, naphthoquinones, triterpenes, Psychotria stachyoides IntroductionIndole alkaloids represent the biggest single class of all alkaloids from plants. The major groups under investigation are the ones with monoterpene (C 10 ) or nor-monoterpene (C 9 ) moieties joined to the tryptamine, which are distributed on a wide range of different structures in the Apocynaceae, Loganiaceae, Nyssaceae and Rubiaceae families. The genus Psychotria (Rubiaceae) comprises more than 1000 species distributed in tropical regions worldwide. This genus is taxonomically complex, and is particularly characterized as a prolific source of bioactive polyindole and monoterpenoid indole alkaloids. Previous phytochemical studies of species of Psychotria from the Southern Brazil have revealed the remarkable presence of glycosylated indole monoterpenoid alkaloids. 1As part of the investigative efforts to find alkaloids from Rubiaceae species of the Northeastern Brazil flora, Psychotria stachyoides (subgroup Heteropsychotria), a shrub growing predominantly in tropical and sub-tropical forests from Brazil (where it is popularly named as "erva-d'anta"), 2 has been investigated. This work reports the isolation and structural characterization of the new glucosilated monoterpene indole alkaloid named as N-demethylcorreantoside (1) from the leaves of P. stachyoides, in addition to the known bizantionoside B and a-amyrin. ) functionalities. From the 1 H NMR spectrum, a tetrahydro-b-carboline system was defined by Pimenta et al. 2217 Vol. 22, No. 11, 2011 the typical aromatic signals at d 7.22 (td, J 7.4 and 1.0 Hz, H-10), 7.26 (td, J 7.4 and 1.3 Hz, H-11), 7.45 (dd, J 7.4 and 1.3 Hz, H-9), 8.15 (dd, J 7.4 and 1.0 Hz, H-12), besides the two methylenes at d 3.10 (t, J 5.5 Hz, 2H-5) and 2.70 (t, J 5.4 Hz, 2H-6). 10 The 1 H NMR spectrum also showed signals relative to an iridoid unit related to a secologanin moiety due to the signals of the olefinic hydrogen at d 5.85 (ddd, J 17.6, 10.0 and 7.6 Hz, H...

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(1)H and (13)C NMR chemical shifts of praecansone B, pongaflavone and dehydrorotenone isolated from Tephrosia egregia Sandw and obovatin from T. toxicaria Pers. were unambiguously assigned by 1D and 2D NMR experiments including (1)H, (1)H COSY, gHMQC and gHMBC, allowing the correction of literature assignments.

Red angico is a heteropolysaccharide (arabinogalactan) obtained from Anadenanthera macrocarpa trees. Carboxymethylation of angico gum (AG) with monochloroacetic acid (MCA) in alkaline aqueous medium resulted in samples which were characterized by 13 C nuclear magnetic resonance spectroscopy and gel permeation chromatography. The effects of reaction parameters, such as alkali concentration, MCA/AG ratio and temperature on the reaction yield and degree of substitution (DS) were investigated. The DS and MCA total efficiency values increase up to 2 h reaction time and then decrease. The DS varied from 0.11 to 1.10 depending on NaOH/MCA/AG ratio and temperature. The highest MCA total efficiency (0.57) was obtained for NaOH/MCA/AG molar ratio equal to 3:1:1, at 708C. (DS ¼ 0.63, yield ¼ 91.0%). Nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC) analysis shows that polymer degradation was observed in all samples.

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We described earlier that an alkaloid-rich fraction (F 3-5 ) from Aspidosperma ulei (Markgr) induces penile erection-like behavioral responses in mice. This study verified a possible relaxant effect of this fraction on isolated rabbit corpus cavernosum (RbCC) strips precontracted by phenylephrine (1 lM) or K þ 60 mM. F 3-5 (1-300 lg ml À1 ) relaxed the RbCC strips in a concentration-dependent and reversible manner. The relaxant effect of F 3-5 (100 lg ml À1 ) on phenylephrine contraction was unaffected in the presence of atropine, N-x-nitro-L-arginine methyl ester or 1H-[1,2,4]oxadiazole[4,3-a] quinoxalin-1-one and by preincubation with tetrodotoxin, glibenclamide, apamine and charybdotoxin suggesting that mechanisms other than cholinergic, nitrergic, sGC activation or potassium channel opening are probably involved. However, the phasic component of the contraction induced by K þ 60 mM as well as the maximal contraction elicited by increasing external Ca 2 þ concentrations in depolarized corpora cavernosa was inhibited by F 3-5 . We conclude that F 3-5 relaxes the RbCC smooth muscle, at least in part, through a blockade of calcium influx or its function.