Search

Candida spp. is associated with almost 80% of all nosocomial fungal infections and is considered a major cause of blood stream infections. In humans, Cryptococcosis is a disease of the lungs caused by the fungi Cryptococcus gattii and Cryptococcus neoformans. It can be potentially fatal, especially in immune-compromised patients. In a search for antifungal drugs, Deguelia duckeana extracts were assayed against these two fungi and also against Candida albicans, which causes candidiasis. Hexane branches and CH2Cl2 root extracts as well as the substances 4-hydroxylonchocarpine, 3,5,4′-trimethoxy-4-prenylstilbene and 3′,4′-methylenedioxy-7-methoxyflavone were assayed to determine the minimal inhibitory concentration. Phytochemical study of CH2Cl2 root and hexane branch extracts from D. duckeana A.M.G. Azevedo, Fabaceae, resulted in the isolation and characterization of nine phenolic compounds: 4-hydroxyderricine, 4-hydroxylonchocarpine, 3′,4′,7-trimethoxy-flavonol, 5,4′-dihydroxy-isolonchocarpine, 4-hydroxyderricidine, derricidine, 3,5,4′-trimethoxy-stilbene, 3′,4′,7-trimethoxyflavone and yangambin. The only active extract was a CH2Cl2 root showing minimal inhibitory concentration 800 μg/ml against C. gattii, and the investigation of compounds obtained from this extract showed that 4-hydroxylonchocarpine was active against all three fungi (C. neoformans, C. gattii and C. albicans). These results suggest that D. duckeana extracts have potential therapeutic value for the treatment of pathogenic fungi. Keywords: Amazonian plant, Chalcone, Flavonoid, Lignan, Stilbene, Timbó

The objective of this study was to investigate the structural requirements necessary for inhibition of glutathione S-transferase P1-1 (GSTP1-1) and GS-X pump (MRP1 and MRP2) activity by structurally related flavonoids, in GSTP1-1 transfected MCF7 cells (pMTG5). The results reveal that GSTP1-1 activity in MCF7 pMTG5 cells can be inhibited by some flavonoids. Especially galangin was able to inhibit almost all cellular GSTP1-1 activity upon exposure of the cells to a concentration of 25 muM. Other flavonoids like kaempferol, eriodictyol and quercetin showed a moderate GSTP1-1 inhibitory potential. For GSTP1-1 inhibition, no specific structural requirements necessary for potent inhibition could be defined. Most flavonoids appeared to be potent GS-X transport inhibitors with IC50 values ranging between 0.8 and 8 muM. Luteolin and quercetin were the strongest inhibitors with IC50 values of 0.8 and 1.3 muM, respectively. Flavonoids without a C2-C3 double bond like eriodictyol, taxifolin and catechin did not inhibit GS-X pump activity. The results of this study demonstrate that the structural features necessary for high potency GS-X pump inhibition by flavonoids are (1) the presence of hydroxyl groups, especially two of them generating the 3',4-catechol moiety; and (2) a planar molecule due to the presence of a C2-C3 double bond. Other factors, like lipophilicity and the total number of hydroxyl groups do not seem to be dominating the flavonoid-mediated GS-X pump inhibition. To identify the GS-X pump responsible for the DNP-SG efflux in MCF7 cells, the effects of three characteristic flavonoids quercetin, flavone and taxifolin on MRP1 and MRP2 activity were studied using transfected MDCKII cells. All three flavonoids as well as the typical MRP inhibitor (MK571) affected MRP1-mediated transport activity in a similar way as observed in the MCF7 cells. In addition, the most potent GS-X pump inhibitor in the MCF7 cells, quercetin, did not affect MRP2-mediated transport activity. These observations clearly indicate that the GS-X pump activity in the MCF7 cells is likely to be the result of flavonoid-mediated inhibition of MRP1 and not MRP2. Altogether, the present study reveals that a major site for flavonoid interaction with GSH-dependent toxicokinetics is the GS-X pump MRP1 rather than the conjugating GSTP1-1 activity itself. Of the flavonoids shown to be most active especially quercetin is frequently marketed in functional food supplements. Given the physiological levels expected to be reached upon supplement intake, the IC50 values of the present study point at possible flavonoid-drug and/or flavonoid-xenobiotic interactions especially regarding transport processes involved in toxicokinetics. (C) 2004 Elsevier Inc. All rights reserved.

Selected flavonoids were tested for their ability to inhibit the catalytic activity of DNA topoisomerase (topo) I and II. Myricetin, quercetin, fisetin, and morin were found to inhibit both enzymes, while phloretin, kaempferol, and 4',6,7-trihydroxyisoflavone inhibited topo II without inhibiting topo I. Flavonoids demonstrating potent topo I and II inhibition required hydroxyl group substitution at the C-3, C-7, C-3', and C-4' positions and also required a keto group at C-4. Additional B-ring hydroxylation enhanced flavonoid topo I inhibitory action. A C-2,C-3 double bond was also required, but when the A ring is opened, the requirement for the double bond was eliminated. Genistein has been previously reported to stabilize the covalent topo II-DNA cleavage complex and thus function as a topo II poison. All flavonoids were tested for their ability to stabilize the cleavage complex between topo I or topo II and DNA. None of the agents stabilized the topo I-DNA cleavage complex, but prunetin, quercetin, kaempferol, and apigenin stabilized the topo II DNA-complex. Competition experiments have shown that genistein-induced topo II-mediated DNA cleavage can be inhibited by myricetin, suggesting that both types of inhibitors (antagonists and poisons) interact with the same functional domain of their target enzyme. These results are of use for the selection of flavonoids that can inhibit specific topoisomerases at specific stages of the topoisomerization reaction. © 1995, American Chemical Society. All rights reserved. 58 217 225 Tradenames: vm 26, bristol myers squibb, United States vp 16, bristol myers squibb, United States Manufacturers: aldrich, United States bristol myers squibb, United States gibco, United States sigma, United States Cited By :222

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:22:49Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:38:11Z : No. of bitstreams: 1 2-s2.0-49649127665.pdf: 191238 bytes, checksum: 1bc56fd6d4260980c0f9aecf463776e6 (MD5) Made available in DSpace on 2014-05-27T11:22:49Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-03-01 Eriocaulaceae is a pantropical family that comprises about 1100 species distributed in 11 genera. The infrafamilial relationships are still unsatisfactorily resolved, because of the tiny flowers and generalized morphology, which makes the taxonomy very difficult. Flavonoid and naphthopyranone profiles have proved to be important in order to contribute to the alignment of genera into the family. We here present a survey of the chemical data of Eriocaulaceae with a discussion about their contribution to the taxonomy of Eriocaulaceae. © 2008 Verlag der Zeitschrift für Naturforschung. Departamento de Ciências Biológicas Faculdade de Ciências UNESP, C.P. 473, 17033-360 Bauru, SP Departamento de Química Orgânica Instituto de Química de Araraquara UNESP, C.P. 355, 14801-970 Araraquara, SP Departamento de Botânica Instituto de Biociências Universidade de São Paulo, C.P. 11461, 05427-970 São Paulo, SP Departamento de Ciências Biológicas Faculdade de Ciências UNESP, C.P. 473, 17033-360 Bauru, SP Departamento de Química Orgânica Instituto de Química de Araraquara UNESP, C.P. 355, 14801-970 Araraquara, SP

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:19:50Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:39:33Z : No. of bitstreams: 1 2-s2.0-0033298456.pdf: 742023 bytes, checksum: cd347e4e5e0c0c14bdbee9e1b0b725a1 (MD5) Made available in DSpace on 2014-05-27T11:19:50Z (GMT). No. of bitstreams: 0 Previous issue date: 1999-12-01 A general procedure was developed for the simultaneous separation of flavonoids and naphthopyrones from the polar extracts of the capitula from Brazilian everlasting plants is described. The ethanolic extracts of several species from the Paepalanthus genus (Eriocaulaceae) were fractionated by droplet countercurrent chromatography followed by column chromatography on pvp and sephadex LH-20. The isolated compounds were identified by spectrometric analysis and comparison with literature data. This approach led to the isolation of 9-O-β-D-glucopyranosylpaepalantine (1), 9-O-β-D-glucopyranosyl (1→6)allopyranosylpaepalantine (2), along with the flavonoids 6-methoxykaempferol (3), 3-O-β-D-glucopyranosyl-6-methoxykaempferol (4), patuletin (5), 3-Oβ-D-rutinosylpatuletin (6), 7-O-β-D-glucopyranosylquercetagetin (7), 5,7,4'-trihydroxy-6,3'-dimethoxyflavone (8) and 5,7,4'-trihydroxy-6,3'-dimethoxyflavonol (9). Departamento de Quimica Organica UNESP, C.P. 355, 14800-900 - Araraquara - SP Departamento de Quimica Organica UNESP, C.P. 355, 14800-900 - Araraquara - SP