Antifungal activity of schinol and a new biphenyl compound isolated from Schinus terebinthifolius against the pathogenic fungus Paracoccidioides brasiliensis

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to isolate and identify the antifungal compounds from the extracts of <it>Schinus terebinthifolius </it>(Anacardiaceae) against clinical isolates of the pathogenic fungus <it>Paracoccidioides brasiliensis</it>.</p> <p>Methods</p> <p>The hexane and dichlomethane fractions from leaves and stems of <it>S. terebinthifolius </it>were fractionated using several chromatography techniques to afford four compounds.</p> <p>Results</p> <p>The compounds isolated from <it>S. terebinthifolius </it>were identified as schinol (<b>1</b>), a new biphenyl compound, namely, 4'-ethyl-4-methyl-2,2',6,6'-tetrahydroxy[1,1'-biphenyl]-4,4'-dicarboxylate (<b>2</b>), quercetin (<b>3</b>), and kaempferol (<b>4</b>). Compounds <b>1 </b>and <b>2 </b>were active against different strains of <it>P. brasiliensis</it>, showing a minimal inhibitory concentration value against the isolate Pb B339 of 15.6 μg/ml. The isolate Pb 1578 was more sensitive to compound <b>1 </b>with a MIC value of 7.5 μg/ml. Schinol presented synergistic effect only when combined with itraconazole. The compounds isolated from S. <it>terebinthifolius </it>were not able to inhibit cell wall synthesis or assembly using the sorbitol assay.</p> <p>Conclusion</p> <p>This work reveals for the first time the occurrence of compound <b>2 </b>and discloses activity of compounds <b>1 </b>and <b>2 </b>against several clinical isolates of <it>P. brasiliensi</it>s. These results justify further studies to clarify the mechanisms of action of these compounds.</p

In vitro leishmanicidal, antibacterial and antitumour potential of anhydrocochlioquinone A obtained from the fungus Cochliobolus sp

The bioassay-guided fractionation of the ethyl acetate extract of the fungus Cochliobolus sp. highlighted leishmanicidal activity and allowed for anhydrocochlioquinone A (ANDC-A) isolation. MS, 1D and 2D NMR spectra of this compound were in agreement with those published in the literature. ANDC-A exhibited leishmanicidal activity with EC50value of 22.4 \uc2\ub5g/mL (44 \uce\ubcM) and, when submitted to the microdilution assay against Gram-positive and Gram-negative bacteria, showed a minimal inhibitory concentration against Staphylococcus aureus ATCC 25295 of 128 \uce\ubcg/mL (248.7 \uce\ubcM). It was also active against five human cancer cell lines, showing IC50values from 5.4 to 20.3 \uce\ubcM. ANDC-A demonstrated a differential selectivity for HL-60 (SI 5.5) and THP-1 (SI 4.3) cell lines in comparison with Vero cells and was more selective than cisplatin and doxorubicin against MCF-7 cell line in comparison with human peripheral blood mononuclear cells. ANDC-A was able to eradicate clonogenic tumour cells at concentrations of 20 and 50 \uce\ubcM and induced apoptosis in all tumour cell lines at 20 \uce\ubcM. These results suggest that ANDC-A might be used as a biochemical tool in the study of tumour cells biochemistry as well as an anticancer agent with durable effects on tumours

Leishmanicidal Metabolites from Cochliobolus sp., an Endophytic Fungus Isolated from Piptadenia adiantoides (Fabaceae)

Protozoan parasites belonging to genera Leishmania and Trypanosoma are the etiological agents of severe neglected tropical diseases (NTDs) that cause enormous social and economic impact in many countries of tropical and sub-tropical areas of the world. In our screening program for new drug leads from natural sources, we found that the crude extract of the endophytic fungus Cochliobolus sp. (UFMGCB-555) could kill 90% of the amastigote-like forms of Leishmania amazonensis and inhibit by 100% Ellman's reagent reduction in the trypanothione reductase (TryR) assay, when tested at 20 µg mL−1. UFMGCB-555 was isolated from the plant Piptadenia adiantoides J.F. Macbr (Fabaceae) and identified based on the sequence of the internally transcribed spacer (ITS) regions of its ribosomal DNA. The chromatographic fractionation of the extract was guided by the TryR assay and resulted in the isolation of cochlioquinone A and isocochlioquinone A. Both compounds were active in the assay with L. amazonensis, disclosing EC50 values (effective concentrations required to kill 50% of the parasite) of 1.7 µM (95% confidence interval = 1.6 to 1.9 µM) and 4.1 µM (95% confidence interval = 3.6 to 4.7 µM), respectively. These compounds were not active against three human cancer cell lines (MCF-7, TK-10, and UACC-62), indicating some degree of selectivity towards the parasites. These results suggest that cochlioquinones are attractive lead compounds that deserve further investigation aiming at developing new drugs to treat leishmaniasis. The findings also reinforce the role of endophytic fungi as an important source of compounds with potential to enter the pipeline for drug development against NTDs

Flavonoids from leaves of Mauritia flexuosa

The chromatographic fractionation of the Mauritia flexuosa L. f., Arecaceae, leaves extract, a plant known by the name of buriti palm tree, resulted in the isolation of six flavonoids: tricin-7-O-rutinoside, apigenin-6-C-arabinoside, 8-C-glucoside (isoschaftoside), kaempferol-3-O-rutinoside (nicotiflorine), quercetin-3-O-rutinoside (rutin), luteolin-8-C-glucoside (orientin) and luteolin-6-C-glucoside (isoorientin). The flavonoids were found out and previously reported as constituents of the Arecaceae family plants, but the occurrence of C-glucoside flavonoids, in the species being analyzed, is described for the first time on this study. The structural elucidations of all of the isolated compounds were performed by means of the comparison of their spectral data (1H and 13C NMR, UV and ESI-MS) with those ones of the literature. Keywords: Arecaceae, flavonoids, Mauritia flexuos

Chemical constituents of Habenaria petalodes Lindl. (Orchidaceae)

Habenarioside, a new natural product identified as [(2R)-2-[(2,3,4,6-tetra-O-acetyl-&#946;-D-glucopyranosyl)oxy]-2-(2-methylpropyl)-1,4-dioxo-1,4-butanediyl]bis(oxymethylene-4,1-phenylene) bis-&#946;-D-glucopyranoside, along with two known related metabolites, loroglossin and militarin, were isolated from the ethanol extract of the whole plant Habenaria petalodes Lindl. (Orchidaceae). The flavonoids isoquercitrin, isorhamnetin 3-O-&#946;-D-glucopyranoside, and isorhamnetin 3,7-di-O-&#946;-D-glucopyranoside were also isolated. The structures of all compounds were established by analysis of their MS, IR, UV, 1D and 2D NMR spectra, and comparison with published data

Chemical constituents and leishmanicidal activity from leaves of Kielmeyera variabilis

Many phenolic compounds such as xanthones, quinones and coumarins have been isolated from Kielmeyera species; however the presence of flavonoids have been showed in other genera in the Calophylleae tribe as Caraipa, Mesua and Calophyllum. Six known glycosidic flavonoids: quercetin 3-&#946;-O-galactopyranoside (1), quercetin 3-&#946;-O-glucopyranoside (2), quercetin 3-O-&#945;-rhamnoside (3), luteolin 6-C-&#946;-glucopyranoside (4), isovitexin (5), kaempferol 3-O-&#945;-rhamnoside (6) and one triterpene, lupenone (7) were isolated, for the first time, from organic crude extract of Kielmeyera variabilis Mart. &amp; Zucc., Calophyllaceae, leaves. The crude organic extract from K. variabilis leaves exhibited 95% of leishmanidal activity at 20 µg/mL on amastigote-like form of Leishmania (Leishmania) amazonensis in vitro model and only compound 3 showed 40-45% of growth inhibition at concentration ranging from 0.78 to 20 µg/mL. In addition, quercetin 3-O-&#945;-rhamnoside (quercitrin) was found to be the major metabolite. Our results and previous reports suggest that synergistic effects of flavonoid glycosides are the cause of significant leishmanidal activity of the crude organic extract from K. variabilis leaves