Papers by Cecilia Oliveira
Quaternary �-carboline alkaloids from Psychotria prunifolia (Kunth) Steyerm
Phytochem Lett, 2010
Secondary metabolites of Hyptis ovalifolia Benth (Lamiaceae)
Mode of action of the natural product argentilactone on Paracoccidoidides brasiliensis Pb01 isolate: Molecular docking, proteomic and transcriptional analysis
Paracoccidioidomycosis (PCM) is an important endemic mycosis in Latin America, caused by the fung... more Paracoccidioidomycosis (PCM) is an important endemic mycosis in Latin America, caused by the fungus Paracoccidioides genus. The treatment of PCM is long and the resistance to antimicrobial drugs interferes with therapeutic efficacy. Thus, it is necessary to discover and develop new antifungal agents. Plants compounds have a great structural diversity; many of them are models for the synthesis of a huge number of drugs. Argentilactone, the major constituent of essential oil of Hyptis ovalifolia, is known to suppress proliferation of fungi. The aim of this work was investigate the action of argentilactone on Pb01 isolate. Argentilactone inhibited Pb01 yeast cells growth and influenced in the transition from mycelium to yeast. Argentilactone and reduced argentilactone displayed a potent inhibitory activity against both recombinant and native isocitrate liase, PbICL. The ability of argentilactone and derivatives to bind to PbICL was investigated. The study was based on homology modeling...
Studies of Molecular Docking between Argentilactona and Isocitrate Lyase of Paracoccidioides brasiliensis
The fungus Paracoccidioides brasiliensis is the etiological agent of paracoccidioidomycosis (PCM)... more The fungus Paracoccidioides brasiliensis is the etiological agent of paracoccidioidomycosis (PCM), a systemic human mycosis being the eighth most common cause of death among chronic infections. The treatment of PCM is long and requires high doses of antifungal agents. Thus, there is currently a great interest in developing new antifungal agents. The toxicity of drugs and appearance of resistant strains have imposition the search for new therapeutic approaches. The protein isocitrate lyase from P. Brasiliensis (ICL_Pb) is an enzyme that is directly related to the virulence of pathogenic fungi. Recent studies have revealed the inhibitory action of argentilactone, a natural compounds extracted from the essential oil of Hyptis ovalifolia. In this work, our goal is to understand how the interaction of this molecule occurs with ICL_Pb. For this, we describe the study of molecular docking to investigate the ability of the argentilactona molecule to bind to the active site of ICL_Pb. The st...
Virtual Screening for Isocitrate Lyase of Paracoccidioides brasiliensis: An exhaustive analysis using AutoDock VINA
The fungus Paracoccidioides brasiliensis is the agent of paracoccidioidomycosis (PCM) that can ca... more The fungus Paracoccidioides brasiliensis is the agent of paracoccidioidomycosis (PCM) that can cause pulmonary mycosis and can be acquired by inhalation of fungal airbone propagules that can disseminate to several organs and tissues leading to a severe form of the disease. The protein Isocitrate Lyase from P. Brasiliensis (ICL_Pb) is an enzyme that is directly related to the virulence of pathogenic fungi and its structure has not yet been resolved. In this paper we describe a study performed to develop rational ligands as candidates for inhibit ICL_Pb. We present an important step in search of ligands based on homology modeling, molecular dynamics and molecular docking involving Virtual Screening (VS) through the program AutoDock Vina (ADVina). Were identified from the database of natural compounds (data bank ZINC) ligands as strong candidates to inhibit the activity of ICL_Pb when compared to the original ligand (molecule isocitrate). This process involved two stages: (i) the selec...
Revista Brasileira de Farmacognosia, 2010
A atividade antioxidante, avaliada pelo método DPPH (1,1-difenil-2-picrilidrazila), e o teor em c... more A atividade antioxidante, avaliada pelo método DPPH (1,1-difenil-2-picrilidrazila), e o teor em compostos fenólicos totais do extrato bruto metanólico e frações das folhas da espécie Palicourea rigida Kunth, Rubiaceae, foram quantificadas neste trabalho. Apesar da baixa atividade apresentada pelo extrato bruto (500 ppm), a fração acetato de etila apresentou atividade moderada (192 ppm) e o maior teor de fenólicos totais dentre as frações ensaiadas. Assim, a fração acetato de etila foi submetida a procedimentos cromatográficos o que resultou no isolamento dos flavonoides quercetina 3-O-β-D-glicosídeo, quercetina 3-O-soforosídeo e isoraminetina 3-glicosídeo, cujas estruturas foram elucidadas por análise espectroscópica, incluindo RMN (1D e 2D) e comparação com os dados da literatura.
BMC Complementary and Alternative Medicine, 2014
The great potential of plants as Hymenaea courbaril L (jatoba) has not yet been throughly explore... more The great potential of plants as Hymenaea courbaril L (jatoba) has not yet been throughly explored scientifically and therefore it is very important to investigate their pharmacological and toxicological activities to establish their real efficacy and safety. This study investigated the cytotoxicity of xylem sap of Hymenaea courbaril L and its bioactivity against the fungi Cryptococcus neoformans species complex and dermatophytes. The fresh xylem sap of H. courbaril was filtered resulting in an insoluble brown color precipitate and was identified as fisetin. In the filtrate was identified the mixture of fisetinediol, fustin, 3-O-methyl-2,3-trans-fustin and taxifolin, which were evaluated by broth microdilution antifungal susceptibility testing against C. neoformans species complex and dermatophytes. The fresh xylem sap and fisetin were screened for cytotoxicity against the 3T3-A31 cells of Balb/c using neutral red uptake (NRU) assay. The fresh xylem sap and the fisetin showed higher in vitro activity than the filtrate. The xylem sap of H. courbaril inhibited the growth of dermatophytes and of C. neoformans with minimal inhibition concentration (MIC) < 256 μg/mL, while the fisetin showed MIC < 128 μg/mL for these fungi. Fisetin showed lower toxicity (IC 50 = 158 μg/mL) than the fresh xylem sap (IC 50 = 109 μg/mL). Naturally occurring fisetin can provide excellent starting points for clinical application and can certainly represent a therapeutic potential against fungal infections, because it showed in vitro antifungal activity and low toxicity on animal cells.
BMC Complementary and Alternative Medicine, 2014
The great potential of plants as Hymenaea courbaril L (jatoba) has not yet been throughly explore... more The great potential of plants as Hymenaea courbaril L (jatoba) has not yet been throughly explored scientifically and therefore it is very important to investigate their pharmacological and toxicological activities to establish their real efficacy and safety. This study investigated the cytotoxicity of xylem sap of Hymenaea courbaril L and its bioactivity against the fungi Cryptococcus neoformans species complex and dermatophytes. The fresh xylem sap of H. courbaril was filtered resulting in an insoluble brown color precipitate and was identified as fisetin. In the filtrate was identified the mixture of fisetinediol, fustin, 3-O-methyl-2,3-trans-fustin and taxifolin, which were evaluated by broth microdilution antifungal susceptibility testing against C. neoformans species complex and dermatophytes. The fresh xylem sap and fisetin were screened for cytotoxicity against the 3T3-A31 cells of Balb/c using neutral red uptake (NRU) assay. The fresh xylem sap and the fisetin showed higher in vitro activity than the filtrate. The xylem sap of H. courbaril inhibited the growth of dermatophytes and of C. neoformans with minimal inhibition concentration (MIC) < 256 μg/mL, while the fisetin showed MIC < 128 μg/mL for these fungi. Fisetin showed lower toxicity (IC 50 = 158 μg/mL) than the fresh xylem sap (IC 50 = 109 μg/mL). Naturally occurring fisetin can provide excellent starting points for clinical application and can certainly represent a therapeutic potential against fungal infections, because it showed in vitro antifungal activity and low toxicity on animal cells.
PLoS ONE, 2014
The dimorphic fungus Paracoccidioides spp. is responsible for paracoccidioidomycosis, the most pr... more The dimorphic fungus Paracoccidioides spp. is responsible for paracoccidioidomycosis, the most prevalent systemic mycosis in Latin America, causing serious public health problems. Adequate treatment of mycotic infections is difficult, since fungi are eukaryotic organisms with a structure and metabolism similar to those of eukaryotic hosts. In this way, specific fungus targets have become important to search of new antifungal compound. The role of the glyoxylate cycle and its enzymes in microbial virulence has been reported in many fungal pathogens, including Paracoccidioides spp. Here, we show the action of argentilactone and its semi-synthetic derivative reduced argentilactone on recombinant and native isocitrate lyase from Paracoccidioides lutzii Pb01 (PbICL) in the presence of different carbon sources, acetate and glucose. Additionally, argentilactone and its semi-synthetic derivative reduced argentilactone exhibited relevant inhibitory activity against P. lutzii Pb01 yeast cells and dose-dependently influenced the transition from the mycelium to yeast phase. The other oxygenated derivatives tested, epoxy argentilactone and diol argentilactone-, did not show inhibitory action on the fungus. The results were supported by in silico experiments.
Química Nova, 2012
pohliana Müll. Arg. (RUBIACEAE). This phytochemical investigation of Guettarda pohliana leaves le... more pohliana Müll. Arg. (RUBIACEAE). This phytochemical investigation of Guettarda pohliana leaves led to the isolation of the triterpenes pomolic acid, rotundic acid, 3b,6a,19a,23-tetrahydroxyurs-12-en-28-oic acid, clethric acid, ursolic acid and oleanolic acid, the monoterpenoids loliolide and secoxyloganin, besides daucosterol and steroids. The structures of the isolated compounds were assigned on the basis of NMR data, including two-dimensional NMR methods. The anti-inflammatory activity of the crude methanolic extracts from leaves and roots, as well as of their fractions, was evaluated.
Glucosidic iridoids from Molopanthera paniculata Turcz. (Rubiaceae, Posoquerieae)
Phytochemistry Letters, 2012
ABSTRACT
Phytochemistry, 2013
Thirteen Psychotria alkaloids were evaluated regarding their interactions with acetylcholinestera... more Thirteen Psychotria alkaloids were evaluated regarding their interactions with acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and monoamine oxidases A and B (MAO-A and MAO-B), which are enzymatic targets related with neurodegenerative diseases. Two quaternary b-carboline alkaloids, prunifoleine and 14-oxoprunifoleine, inhibited AChE, BChE and MAO-A with IC 50 values corresponding to 10 and 3.39 lM for AChE, 100 and 11 lM for BChE, and 7.41 and 6.92 lM for MAO-A, respectively. Both compounds seem to behave as noncompetitive AChE inhibitors and time-dependent MAO-A inhibitors. In addition, the monoterpene indole alkaloids (MIAs) angustine, vallesiachotamine lactone, E-vallesiachotamine and Z-vallesiachotamine inhibited BChE and MAO-A with IC 50 values ranging from 3.47 to 14 lM for BChE inhibition and from 0.85 to 2.14 lM for MAO-A inhibition. Among the tested MIAs, angustine is able to inhibit MAO-A in a reversible and competitive way while the three vallesiachotamine-like alkaloids display a time-dependent inhibition on this target. Docking calculations were performed in order to understand the binding mode between the most active ligands and the selected targets. Taken together, our findings established molecular details of AChE, BChE and MAO-A inhibition by quaternary b-carboline alkaloids and MIAs from Psychotria, suggesting these secondary metabolites are scaffolds for the development of multifunctional compounds against neurodegeneration.
Cytotoxic activity ofGuettarda pohlianaMüll. Arg. (Rubiaceae)
Natural Product Research, 2013
The cytotoxic activity of crude extracts and their fractions from leaves and roots of G. pohliana... more The cytotoxic activity of crude extracts and their fractions from leaves and roots of G. pohliana was assessed against nine human cancer cell lines: melanoma (UACC-62), breast (MCF-7), breast expressing the multidrug resistance phenotype (NCI-ADR), lung (NCI-460), prostate (PCO-3), kidney (786-0), ovarian (OVCAR), colon (HT-29) and leukaemia (K-562). The hexane fraction from leaves (HL) and ethyl acetate (EAR), chloroform (CR) and hydromethanolic (HMR) fractions from roots were the most active fractions against K-562 with GI₅₀ values being lower than 1 μg mL⁻¹. Also, CR and HMR fractions were active against UACC-62 cell line in the same order of magnitude. The phytochemical study of the CR fraction allowed identifying the known iridoids secoxyloganin, sweroside and loganin.
Journal of the Brazilian Chemical Society, 2007
Dois novos diterpenos do tipo abietano 3β-hidroxi-9α, 13α-epidioxiabiet-8(14)-eno (1) e 3-oxo-9α,... more Dois novos diterpenos do tipo abietano 3β-hidroxi-9α, 13α-epidioxiabiet-8(14)-eno (1) e 3-oxo-9α,13α-epidioxiabiet-8(14)-eno (2) foram isolados do extrato bruto metanólico dos pecíolos de Sagittaria montevidensis ssp montevidensis (Alismataceae). As estruturas de 1 e 2 foram determinadas com base em análises espectrométricas do tipo EM-AR, IV, bem como, RMN de 1 H e 13 C uni e bi dimensionais. Two new abietane-type diterpenes, 3β-hydroxy-9α, 13α-epidioxyabiet-8(14)-ene (1) and 3-oxo-9α,13α-epidioxyabiet-8(14)-ene (2), were isolated from the methanolic crude extract of the petioles of Sagittaria montevidensis ssp montevidensis (Alismataceae). The structures of 1 and 2 were determined on the basis of spectrometric analyses including HREIMS, IR as well as 1 H and 13 C 1 and 2D NMR.
Synthesis and absolute stereochemistry of the bicyclic goniofupyranone core
Journal of Molecular Structure, 2013
Abstract A bicyclic goniofupyranone core was synthesized from argentilactone using epoxide as an ... more Abstract A bicyclic goniofupyranone core was synthesized from argentilactone using epoxide as an intermediate. The absolute stereochemistry of all asymmetric centers of a compound possessing the 2,6-dioxabicyclo [3.2.1]-octan-3-one moiety were unambiguously determined directly from X-ray data for the first time. Additionally, the absolute stereochemistry of the major epoxide was reported.
Journal of Ethnopharmacology, 2000
The essential oil from the hydrodistillation of Eugenia dysenterica leaves consisted mainly of b-... more The essential oil from the hydrodistillation of Eugenia dysenterica leaves consisted mainly of b-caryophyllene and a-humulene as the major sesquiterpene, while limonene and a-thujene were the major monoterpene hydrocarbons. The main oxygenated mono and sesquiterpene constituents were a-terpineol and b-caryophyllene oxide, respectively. The oil was investigated against eight strains of Candida albicans, 35 strains of Cryptococcus neoformans var. neoformans, and two C. neoformans var. gattii isolated from HIV-infected individuals with candidosis or cryptococcal meningitis using the agar dilution method. Based on the minimal inhibitory concentration (MIC) values, the most significant results were obtained against Cryptococcus strains. It was observed that 22 strains were inhibited at a concentration of 250 mg/ml, whereas four exhibited potent inhibition with MIC values below 125 mg/ml against 10 6 UFC/ml organisms. We found MICs ] 3.12 mg/ml for 91.6, 50 and 30% of all Cryptococcus strains in relation of amphotericin B, fluconazole and itraconazole, respectively.
Food and Chemical Toxicology, 2012
Essential oil (EO) of Alpinia zerumbet leaves, at non-toxic concentrations (50-300 lg/mL), did no... more Essential oil (EO) of Alpinia zerumbet leaves, at non-toxic concentrations (50-300 lg/mL), did not induce genotoxicity in human leukocytes. However, at the highest concentration (500 lg/mL) tested caused a reduction in cell proliferation and viability, and an increase in DNA damage. Moreover, in vivo experiments showed that EO (400 mg/kg) did not exert mutagenicity on peripheral blood cells and bone marrow in mice. In DPPH test, EO showed scavenging effects against DPPH radicals, and other free radicals (determination of intracellular GSH and lipid peroxidation assays). Furthermore, EO was able to reduce the intracellular levels of ROS, and prevented leukocytes DNA against oxidative damage. The ability of EO to reduce H 2 O 2 toxicity was observed only when cells were treated with EO during and after exposure to H 2 O 2 . With the co-and post-treatment procedures, EO decreased the frequency of apoptotic and micronucleated leukocytes as well DNA strand breaks. However, a synergistic effect was observed in cultures exposed to 500 lg/mL EO. In conclusion, EO at concentrations up to 300 lg/mL or doses up to 400 mg/kg are not mutagenic in leukocytes and in mice, but do have antioxidative and protective effects against the cytotoxicity and clastogenesis induced by H 2 O 2 .
Journal of the Brazilian Chemical Society, 2012
A continuidade do estudo fitoquímico de P. prunifolia com a análise dos extratos etanólicos obtid... more A continuidade do estudo fitoquímico de P. prunifolia com a análise dos extratos etanólicos obtidos a partir de suas raízes e galhos levou ao isolamento de cinco alcaloides indol-b-carbolínicos dos quais, dois derivados, o 10-hidróxi-iso-deppeaninol e o N-óxido-10-hidróxi-antirhina são descritos pela primeira vez. As estruturas foram determinadas por análise de técnicas espectroscópicas de IV, EMAR e RMN (1 H e 13 C, 1D e 2D). A avaliação da atividade frente à Leishmania amazonensis e Trypanosoma cruzi, mostrou que os extratos brutos e os alcaloides 14-oxoprunifoleína e estrictosamida inibiram as formas promastigotas de L. amazonensis, com valores de CI 50 de 16,0 e 40,7 mg per mL, respectivamente. The continuity of the phytochemical study of crude extracts of P. prunifolia's roots and branches led to the isolation of five indole-b-carboline alkaloids. Among them, the 10-hydroxyiso-deppeaninol and N-oxide-10-hydroxy-antirhine derivatives are described here for the first time. The structures were achieved through 1D and 2D NMR, IR and HRMS analyses. The branches and roots crude extracts and the alkaloids 14-oxoprunifoleine and strictosamide showed selective activity against L. amazonensis, with IC 50 values of 16.0 and 40.7 mg per mL, respectively.
Corrigendum to ‘Synthesis and absolute stereochemistry of the bicyclic goniofupyranone core’ [Journal of Molecular Structure 1035C (2013) 448–454]
Journal of Molecular Structure, 2013
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Papers by Cecilia Oliveira