Probing structural properties and antioxidant activity mechanisms for eleocarpanthraquinone.

In this work, we present a computational investigation on the structure and energetics of eleocarpanthraquinone, a newly isolated polyphenolic anthrone-antraquinone. Properties such as bond lengths, angles, atomic charges, bond dissociation enthalpies (BDEs), and ionization potential (IP) were determined through the use of density functional theory (DFT). The B3LYP and M06-2X exchange-correlation functionals were employed along with the 6-31+G(d,p), 6-31+ +G(d,p), and 6-311+G(d,p) basis sets for performing computations in the gas-phase, water, methanol, and ethanol. The conformation presenting all the hydroxyl groups undergoing hydrogen-bond interactions with neighboring oxygen atoms (conformation 5) was assigned as the most stable structure while its counterpart presenting no hydrogen-bond interaction was found to be 36.45 kcal/mol less stable than conformation 5 in the potential energy surface probed at the B3LYP/6-311+G(d,p) level of theory in the gas-phase, for instance. More importantly, the lowest O-H bond dissociation enthalpy was determined to be 93.80 kcal/mol at the B3LYP/6-311+G(d,p) level of theory in water against the 146.58 kcal/mol regarding the IP computed at the same approach, suggesting the hydrogen atom transfer mechanism as being preferred over the single electron transfer mechanism in regards to the antioxidant potential for the case of eleocarpanthraquinone; the same conclusion was drawn from the outcomes of all the other approaches used.

Anti-inflammatory activity of 4',6,7-trihydroxy-5-methoxyflavone from Fridericia chica (Bonpl.) L.G.Lohmann.

Fridericia chica, Bignoniaceae, is a tropical tree-creeper used as a traditional remedy for a number of diseases, highlighting inflammation. Our objective was to corroborate the popular anti-inflammatory use of the hydroethanolic extract from the leaves (HEFc) and of its isolated 4',6,7-trihydroxy-5-methoxyflavone (5-O-methylscutellarein) [1], described here for the first time. Quantitative analysis indicated 8.77 ± 0.23 mg/g of this compound in the extract. Neither HEFc nor [1] was cytotoxic in vitro. In LPS-induced peritonitis in mice, oral pre-treatment with HEFc or [1] led to decreased leukocyte migration to the peritoneal cavity and a reduction in the concentrations of pro-inflammatory cytokines (TNFα and IL-1ß). Also, the anti-inflammatory cytokine IL-10 was enhanced following treatment with [1]. Overall, these results validate the traditional use of Fridericia chica as anti-inflammatory, and indicate that the compound 5-O-methylscutellarein may participate in this effect.

Eglerisine, a Novel Sesquiterpenoid Tropolone from Dulacia egleri with Antiproliferative Effect against an Acute Myeloid Leukemia Lineage.

Chemical investigation of the stems of Dulacia egleri resulted in the isolation of eglerisine (1: ), a compound with a rare sesquiterpenoid tropolone skeleton. Its structure was determined by analysis of spectrometric and spectroscopic data, including HRESIMS, 1D, and 2D NMR. The antiproliferative effects of eglerisine were tested in human leukemia lineages. In the Kasumi-1 lineage, an acute myeloid leukemia cell line, eglerisine reduced cell metabolism, as determined by the resazurin assay. Eglerisine did not induce cell death by either apoptotic or necrotic mechanisms. However, a reduction of the absolute number of cells was observed. Eglerisine induced cell cycle arrest after 72 h of treatment by phosphorylation of H2AX histone, reducing the S phase and increasing the G2 phase of the cell cycle.

4'-Hydroxy-6,7-methylenedioxy-3-methoxyflavone: A novel flavonoid from Dulacia egleri with potential inhibitory activity against cathepsins B and L.

A new flavone, 4'-hydroxy-6,7-methylenedioxy-3-methoxyflavone 1, and two other nucleosides, ribavirin 2 and adenosine 3, were isolated from the leaves of Dulacia egleri. The nucleosides were identified by spectroscopic techniques (1D, 2D-NMR) while the structure of the flavonoid was established by 1D, 2D-NMR analysis, including HRESIMS data. The results obtained in the biological assays showed that the compound 1 was able to inhibit cathepsins B and L with IC50 of 14.88 ±â€¯0.18 µM and 3.19 ±â€¯0.07 µM, respectively. The mechanism of inhibition for both enzymes were determined showing to be competitive at cathepsin B with Ki = 12.8 ±â€¯0.6 µM and non-linear non-competitive with positive cooperativity inhibition at cathepsin L with Ki = 322 ±â€¯33 µM, αKi = 133 ±â€¯15 µM, ßKi = 5.14 ±â€¯0.41 µM and γKi = 13.2 ±â€¯13 µM.

Isovitexin as marker and bioactive compound in the antinociceptive activity of the Brazilian crude drug extracts of Echinodorus scaber and E. grandiflorus

Abstract Echinodorus scaber Rataj and Echinodorus grandiflorus (Cham. & Schltdl.) Micheli, Alismataceae, are popularly used to relieve inflammatory complaints and as diuretic. A study on the antinociceptive effect and selected marker compounds in eleven extracts from different locations was undertaken and their antinociceptive effect was assessed. The fingerprints were compared by HPLC-DAD and the content of vitexin, isovitexin, isoorientin and vitexin-2-O-rhamnoside were determined. All samples presented antinociceptive activity reducing the writhes by 36.4-62.5% and 47.4-79.8% at 10 and 50 mg/kg, respectively; indomethacin (5 mg/kg) reduced writhes by 82.6-90.1%. The content of the flavonoids C-glycosides, however, presented a strong variation. Isovitexin and isoorientin were found in all the samples, with content ranging from traces to 14.70 µg/mg and 2.12-84.27 µg/mg extract, respectively, while vitexin-2-O-rhamnoside occurred in quantifiable amounts only in 3 out of 11 samples ranging from 5.43 to 33.13 µg/mg extract; vitexin was not detected at all or detected in trace amounts. According to the fingerprints, the samples could be arranged in four main groups. All eleven extracts showed antinociceptive activity. Isovitexin was the only flavonoid present in all samples and can be regarded, acting in synergy with the other compounds or not, as the responsible for the antinociceptive activity. Therefore, isovitexin is a good choice as chemical marker when the antinociceptive activity of E. scaber and E. grandiflorus is investigated.

Chemical constituents and antileukemic activity of Eugenia dysenterica.

The study about Eugenia dysenterica led to the isolation of 3-acetyl-urs-12-en-28-oic (1), 3-acetyl-olean-12-en-28-oic acid (2) and isoquercetin (3) from the stem barks, and of 3-O-ß-glucopyranosyl-ß-sitosterol (4), methyl 3-hydroxy-4-methoxybenzoate (5), methyl 4-hydroxyphenyl propionate (6), E-methyl-4-hydroxycinnamate (7), quercetin-3-O-(6ꞌꞌ-O-galloyl)-ß-d-glucopyranoside (8) and quercetin-3-O-ß-d-galactopyranoside (9) from the leaves. The structures 1-9 were set through the analysis of their NMR spectroscopic data. Compounds 2, 3 and 5-8 were reported for the first time in the Eugenia genus. Compound 8 reduced cell viability and presented IC50 values 40.3 and 36.7 µM, for the CCRF-CEM and the Kasumi-1 cells, respectively.

[1-8-NαC]-Zanriorb A1, a Proapoptotic Orbitide from Leaves of Zanthoxylum riedelianum.

A new orbitide named [1-8-NαC]-zanriorb A1 (1) was isolated and characterized from the leaves of Zanthoxylum riedelianum using NMR and mass spectrometry. The absolute configuration of the amino acids was determined using Marfey's method on the acid hydrolysates. Compound 1 induced cell death by apoptosis in Jurkat leukemia T cells (IC50 218 nM).

New iodine derivatives of flavonol and isoflavone.

The reaction of the flavonol 3,7,3', 4'-tetra-O-methylquercetin (1) and of the isoflavone 7,4'-di-O-methylgenistein (2) with alkaline iodine in methanol afforded four new iodine derivatives: 8-iodo-5-hydroxy-3,7,3', 4'-tetramethoxy- flavone (1a) and 6-iodo-5-hydroxy-3,7,3', 4'-tetramethoxyflavone (1b) from 1; 2 afforded a mixture of two compounds, identified as a racemic mixture of (+/-)-trans-5-hydroxy-2,3,7,4'-tetramethoxy-8-iodo-isoflavanone (2a) and (+/-)-trans-5-hydroxy-2,3,7,4'-tetramethoxy-6,8-diiodo-isoflavanone (2b). The formation of these different products reveals a significant difference involving the chemical interaction between the reactive site of alpha, beta-unsaturated ketones of flavonol and isoflavone under the tested reaction conditions (using I2/KOH/MeOH). Furthermore, the trans stereo selectivity is noteworthy in the nucleophylic addition of methanol at the isoflavone alpha, beta-unsaturated system. The structures were identified on the basis of spectral data, mainly 1D and 2D NMR and mass spectra.

A new derivative of dihydroochnaflavone isolated from Luxemburgia species (Ochnaceae) and the complete ¹H and 13C NMR chemical shifts assignments / Um novo derivado da dihidroochnaflavona isolada de Luxemburgia species (Ochnaceae) e o completo assinalamento dos dados de RMN de ¹H e 13C

The biflavonoid 2",3"-dihydroochnaflavone, isolated from the Luxemburgia species (Ochanaceae), was treated with diazomethane to obtain the trimethyl-ether that was treated with pyridine/acetic anhydride to yield a new derivative, 5-acetil-7,4'-dimethyl-flavone-(3'→O-4'")-5"-acetil-7"-methyl-flavanone. The complete ¹H and 13C NMR data assignments of the new derivative were made by the one- and two-dimensional spectral analysis.

O biflavonóide 2",3"-diidroochnaflavona, isolada de espécies de Luxemburgia (Ochanaceae), foi tratada com diazometano e forneceu o éter trimetílico que, em seguida, foi tratado com anidrido acético/piridina obtendo-se um novo derivado, 5-acetil-7,4'-dimetil-flavona-(3'→O-4'")-5"-acetil-7"-metil-flavanona. Fez-se o completo assinalamento dos dados de RMN ¹H e 13C através da análise dos espectros uni- e bidimensionais do derivado.

New iodine derivatives of flavonol and isoflavone

The reaction of the flavonol 3,7,3', 4'-tetra-O-methylquercetin (1) and of the isoflavone 7,4'-di-O-methylgenistein (2) with alkaline iodine in methanol afforded four new iodine derivatives: 8-iodo-5-hydroxy-3,7,3', 4'-tetramethoxy- flavone (1a) and 6-iodo-5-hydroxy-3,7,3', 4'-tetramethoxyflavone (1b) from 1; 2 afforded a mixture of two compounds, identified as a racemic mixture of (±)-trans-5-hydroxy-2,3,7,4'-tetramethoxy-8-iodo-isoflavanone (2a) and (±)-trans-5-hydroxy-2,3,7,4'-tetramethoxy-6,8-diiodo-isoflavanone (2b). The formation of these different products reveals a significant difference involving the chemical interaction between the reactive site of α, β-unsaturated ketones of flavonol and isoflavone under the tested reaction conditions (using I2/KOH/MeOH). Furthermore, the trans stereo selectivity is noteworthy in the nucleophylic addition of methanol at the isoflavone α, β-unsaturated system. The structures were identified on the basis of spectral data, mainly 1D and 2D NMR and mass spectra.

A reação do flavonol 3,7,3',4'-tetra-O-metilquercetina (1) e da isoflavona 7,4'-di-O-metilgenisteina (2) com iodo/KOH em metanol forneceu como produto quatro derivados iodados: 8-iodo-5-hidroxi-3,7,3',4'-tetrametoxiflavona (1a) e 6-iodo-5-hidroxi-3,7,3',4'-tetrametoxiflavona (1b) a partir da iodação de 1; a partir de 2 foi obtida uma mistura racêmica composta de (±)-trans-5-hidroxi-2,3,7,4'-tetrametoxi-8-iodo-isoflavanona (2a) e (±)-trans-5-hidroxi-2,3,7,4'-tetrametoxi-6,8-diiodo-isoflavanona (2b). A formação destes diferentes produtos revela a significante diferença envolvendo a interação química entre o sitio reativo de cetonas α, β-insaturadas de flavonol e de isoflavonas nas condições experimentais testadas (usando I2/KOH/MeOH). Além disso, ressalta-se a estereosseletividade trans na adição de metanol ao sistema α, β-insaturado da isoflavona. As estruturas foram identificadas com análise nos dados espectrométricos de RMN 1D e 2D e massas.

Atividade anti-helmíntica dos flavonóides isolados das raízes de Andira anthelmia (Leguminosae) / Anthelmintic activity of flavonoids isolated from roots of Andira anthelmia (Leguminosae)

As cascas e as raízes de A. anthelmia têm sido utilizadas tradicionalmente como vermífugas. Um estudo biomonitorado do extrato metanólico das raízes de A. anthelmia conduziu ao isolamento das isoflavonas biochanina A e genisteína da fração acetato de etila; biochanina A 7-O-β-D-glicopiranosídeo, biochanina A 7-O-α-L-rhamnopiranosil-(1→6)-β-D-glicopiranosídeo e biochanina A 7-O-β-D-apiofuranosil-(1→5)-β-D-apiofuranosil-(1→6)-β-D-glicopiranosídeo da fração n-butanólica e catequina da fração metanólica. Suas estruturas foram elucidadas com base em dados espectrométricos. A atividade anti-helmíntica foi investigada em camundongos naturalmente infectados por Aspiculuris tetraptera. Os compostos isolados aplicados nos animais por via intragástrica na dose de 2,0 mg.kg-1 durante três dias consecutivos revelaram percentuais significativos na eliminação de A. tetraptera, quando comparados com o lote controle.

Bioactivity-guided fractions of the methanol extract from the roots of Andira anthelmia led the isolation of the isoflavones biochanin A and genistein from the ethyl acetate fraction; biochanin A 7-O-β-D-glucopyranoside, biochanin A 7-O-α-L-rhamnopyranosyl-(1→6)β-D-glucopyranoside and biochanin A 7-O-β-D-apiofuranosyl-(1→5)-β-D-apiofuranosyl-(1→6)β-D-glucopyranoside from the n-butanol fraction and catechin from the methanol one. Their structures were elucidated on the basis of spectroscopy data. The anthelmintic activity was investigated in mice naturally infected by Aspiculuris tetraptera. The compounds administered in the animals by intragastric route in doses of 2.0 mg.kg-1, were effective in the removal of the total number of the A. tetraptera when compared with the control group.