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Abstract The puma population is constantly decreasing, and cloning by somatic cell nuclear transfer can be used to conserve the species. One of the factors determining the success of the development of cloned embryos is the cell cycle stage of the donor cells. We evaluated the effects of full confluency (~100%), serum starvation (0.5% serum), and roscovitine (15 µM) treatments on the cell cycle synchronization in G0/G1 of puma skin-derived fibroblasts by flow cytometric analysis. Also, we assessed the effects of these synchronization methods on morphology, viability, and apoptosis levels using microscopy tools. The results showed that culturing the cells to confluence for 24 h (84.0%), 48 h (84.6%), and 72 h (84.2%) and serum starvation for 96 h (85.4%) yielded a significantly higher percentage of cells arrested in the G0/G1 (P < 0.05) phase than cells not subjected to any cell cycle synchronization method (73.9%). Nevertheless, while serum starvation reduced the percentage of viable cells, no difference was observed for the full confluence and roscovitine treatments (P > 0.05). Moreover, roscovitine for 12 h (78.6%) and 24 h (82.1%) was unable to synchronize cells in G0/G1 (P > 0.05). In summary, full confluency induces puma fibroblast cell cycle synchronization at the G0/G1 stage without affecting cell viability. These outcomes may be valuable for planning donor cells for somatic cell nuclear transfer in pumas.

https://doi.org/10.1590/1984-3143-ar2023-0017

Hydrazones derived from natural aldehydes: in vitro cytotoxic evaluation and in silico pharmacokinetic predictions
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dos Anjos Santos, Victória Laysna

; de Assis Gonsalves, Arlan

; Souza Silva, Maria Franciele

; Evangelista de Oliveira, Fátima de Cássia

; Pinheiro da Costa, Marcília

; Pessoa, Claudia O.

; Melo Araújo, Cleônia Roberta

Revista Colombiana de Ciencias Químico - Farmacéuticas

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Abr 2021, Volume 50 Nº 1 Páginas 217 - 235

Resumo: Es En Pt | Texto: Es En Pt | PDF: Es | PDF: En | PDF: Pt

RESUMEN Introducción: Investigaciones recientes han informado del potencial citotóxico de las hidrazonas contra varias líneas de células cancerosas. Objetivo: Evaluar la actividad anticancerígena in vitro y el perfil farmacocinético de seis compuestos hidrazónicos sintetizados, identificados como vainillina 1-ftalazinilhidrazona (VAN-1); vainillina 2,4-dinitrofenilhidrazona (VAN-2); fenilhidrazona cinamal-dehído (CIN-1); cinamaldehído de isonicotinoil hidrazona (CIN-2); cinamalde-hído 1-ftalazinilhidrazona (CIN-3); y 2,4-dinitrofenilhidrazona cinamaldehído (CIN-4). Se evaluó la actividad citotóxica frente a cuatro líneas celulares cancerosas. Metodología: Los parámetros farmacocinéticos de absorción, distribución, metabolismo, excreción y toxicidad (ADME/T) de las hidrazonas se evaluaron mediante el programa PreADMET. Resultados: Las hidrazonas derivadas del cinamaldehído (CIN-1 y CIN-2) mostraron una alta actividad citotóxica contra las líneas celulares leucémicas (HL-60) y glioblastomas (SF-295). El perfil farmacocinético de las hidrazonas mostró que, en general, las hidrazonas mostraban características satisfactorias de ADME/T. Además, se observó que CIN-2 presentó el perfil in silico más prometedor, presentando alta absorción intestinal, perfil de distribución deseable relacionado con la unión a proteínas plasmáticas, excreción renal adecuada y baja toxicidad. El perfil ADME/T del compuesto CIN-1 destacó su potencial como agente antineoplásico prometedor con acción sobre el SNC, más específicamente contra los glioblastomas.

SUMMARY Introduction: Recent research has reported the cytotoxic potential of hydrazones against various strains of cancer cells. Aim: To evaluate the anticancer activity in vitro and the pharmacokinetic profile of six synthesized hydrazonic compounds, identified as vanillin 1-phthalazinylhydrazone (VAN-1); 2,4-dinitrophenylhydra-zone vanillin (VAN-2); phenylhydrazone cinnamaldehyde (CIN-1); isonicotinoyl hydrazone cinnamaldehyde (CIN-2); cinnamaldehyde 1-phthalazinylhydrazone (CIN-3); and 2,4-dinitrophenylhydrazone cinnamaldehyde (CIN-4). The cytotoxic activity was evaluated against four strains of cancer cells. Methodology: The pharmacokinetic parameters of absorption, distribution, metabolism, excretion, and toxicity (ADME/T) of the hydrazones were evaluated using the PreADMET program. Results: Hydrazones derived from cinnamaldehyde (CIN-1 and CIN-2) showed high cytotoxic activity against leukemic (HL-60) and glioblastomas (SF-295) cell lines. The pharmacokinetic profile of the hydrazones showed that, in general, the hydrazones presented satisfactory characteristics of ADME/T. In addition, it was observed that CIN-2 presented the most promising in silico profile, showing high intestinal absorption, desirable distribution profile related to plasma protein binding, adequate renal excretion, and low toxicity. The ADME/T profile of the CIN-1 compound highlighted its potential as a promising antineoplastic agent with action of the CNS, more specifically against glioblastomas.

RESUMO Introdução: Pesquisas recentes relataram o potencial citotóxico das hidrazonas contra várias linhagens de células cancerígenas. Objetivo: Validara atividade anti-câncer in vitro e o perfil farmacocinético de seis compostos hidrazônicos sintetizados, identificados como vanilina 1-ftalazinil-hidrazona (VAN-1); vanilina 2,4-dinitrofenil-hidrazona (VAN-2); cinnamaldeído de fenil-hidrazona (CIN-1); cinamaldeído isonicotinoil-hidrazona (CIN-2); 1-ftalazinil-hidrazona de cinnamaldeído (CIN-3); e cinamaldeído de 2,4-dinitrofenil-hidrazona (CIN-4). A atividade citotóxica foi avaliada contra quatro linhagens de células cancerígenas. Metodologia: Os parâmetros farmacocinéticos de absorção, distribuição, metabolismo, excreção e toxicidade (ADME/T) das hidrazonas foram avaliados utilizando o programa PreADMET. Resulados: As hidrazonas derivadas do cinnamaldeído (CIN-1 e CIN-2) apresentaram alta atividade citotóxica contra as linhagens celulares leucêmicas (HL-60) e de glioblastomas (SF-295). O perfil farmacocinético das hidrazonas mostrou que, em geral, as hidrazonas apresentaram características satisfatórias de ADME/T. Além disso, observou-se que a CIN-2 apresentou o perfil in silico mais promissor, exibindo alta absorção intestinal, perfil de distribuição desejável relacionado à ligação às proteínas plasmáticas, excreção renal adequada e baixa toxicidade. O perfil ADME/T do composto CIN-1 destacou seu potencial como um agente antineoplásico promissor com ação do SNC, mais especificamente contra glioblastomas.

https://doi.org/10.15446/rcciquifa.v50n1.91232 26 downloads

Relationship between Electrochemical Parameters, Cytotoxicity Data against Cancer Cells of 3-Thio-Substituted Nor-Beta-Lapachone Derivatives. Implications for Cancer Therapy
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Paiva, Yen G. de

; Silva, Thaissa L.

; Xavier, André F. A.

; Cardoso, Mariana F. C.

; Silva, Fernando C. da

; Silva, Maria F. S.

; Pinheiro, Daniel P.

; Pessoa, Claudia

; Ferreira, Vitor F.

; Goulart, Marilia O. F.

Journal of the Brazilian Chemical Society

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Mar 2019, Volume 30 Nº 3 Páginas 658 - 672

Resumo: En | Texto: En | PDF: En

Electrochemical methods are powerful in the characterization and design of redox-modulating agents. We, herein, report the electrochemical investigation, in aprotic medium, of eleven synthetic 3-thio-substituted-nor-beta-lapachones, along with the determination of cytotoxic activity and correspondent selectivity index, against several cancer cell lines and one normal cell. Four of the quinones are novel compounds. The redox behavior is representative of two independent systems: the easy reduction of the quinone moiety and, at far more negative potential, the reductive cleavage of the C-S-C bonding; and the anodic part controlled by the oxidation of the sulfur moiety. The compounds have shown relevant cytotoxic activity, with emphasis on 3-phenyl-thio-2,2-dimethyl-2,3-dihydronaphtho[1,2-b]furan-4,5-dione (compound 2), which mechanism of molecular action was shown to be related to reactive oxygen species (ROS) release. Despite the absence of a linear correlation, there is a trend: the majority of the thionaphthoquinones, with values of first wave reduction potential, less negative than -0.65 V, were active. The less electrophilic compound (3-(cyclohexylthio)-2,2-dimethyl-2,3-dihydronaphtho[1,2-b]furan-4,5-dione, cyclohexyl derivative) is also the less cytotoxic toward cancer cells. Agents containing chalcogens and quinones can be used to attack entities with a disturbed redox balance.

https://doi.org/10.21577/0103-5053.20180248 741 downloads

PHENOLIC DERIVATIVES AND ANTIOXIDANT ACTIVITY OF POLAR EXTRACTS FROM Bauhinia pulchella
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Carvalho, Adonias Almeida

; Santos, Lucivania Rodrigues dos

; Farias, Ruth Raquel Soares de

; Chaves, Mariana Helena

; Feitosa, Chistiane Mendes

; Vieira Júnior, Gerardo Magela

; Araújo, Mônica Regina Silva de

; Ferreira, Paulo Michel Pinheiro

; Pessoa, Claudia do Ó

Química Nova

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Abr 2018, Volume 41 Nº 4 Páginas 405 - 411

Resumo: En | Texto: En | PDF: En

A tea made with the leaves or stem bark of Bauhinia pulchella Benth (Fabaceae) is used in the treatment of diabetes. Ethanol (EEF) and aqueous (EAF) extracts were obtained from the leaves and the antioxidant and citotoxic activities were tested, as well as quantify the content of flavonoids and phenolic compounds (TPC). EEF and EAF showed similar profiles by HPLC, with the presence of three compounds. Column chromatography reverse phase (C18) and Sephadex LH-20, followed by semi preparative HPLC-C18 of EAF resulted in three flavonoids. Their structures were identified by 1H and 13C NMR as myricitrin (1), quercitrin (2) and afzelin (3). In assay of determination of reactive substances to thiobarbituric acid (TBARS), with DPPH, ABTS and nitric oxide (NO•) free radicals, EAF showed antioxidant potential higher than the EEF. This is the first report of the occurrence of the flavonoids 1-3, in the species B. pulchella. EEF and EAF were inactive in the cytotoxicity assays. In short, the polar extracts from the leaves of B. pulchella proved to be promising sources of biomolecules phenolic, with antioxidant potential, which may, in the future, be used as chemical markers for species and validation of therapeutic use.

https://doi.org/10.21577/0100-4042.20170183 1020 downloads

Natural products as new antimitotic compounds for anticancer drug development
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Paier, Carlos Roberto Koscky

; Maranhão, Sarah Sant’Anna

; Carneiro, Teiliane Rodrigues

; Lima, Lídia Moreira

; Rocha, Danilo Damasceno

; Santos, Renan da Silva

; Farias, Kaio Moraes de

; Moraes-Filho, Manoel Odorico de

; Pessoa, Claudia

Clinics

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2018, Volume 73 elocation e813s

Resumo: En | Texto: En | PDF: En

Cell cycle control genes are frequently mutated in cancer cells, which usually display higher rates of proliferation than normal cells. Dysregulated mitosis leads to genomic instability, which contributes to tumor progression and aggressiveness. Many drugs that disrupt mitosis have been studied because they induce cell cycle arrest and tumor cell death. These antitumor compounds are referred to as antimitotics. Vinca alkaloids and taxanes are natural products that target microtubules and inhibit mitosis, and their derivatives are among the most commonly used drugs in cancer therapy worldwide. However, severe adverse effects such as neuropathies are frequently observed during treatment with microtubule-targeting agents. Many efforts have been directed at developing improved antimitotics with increased specificity and decreased likelihood of inducing side effects. These new drugs generally target specific components of mitotic regulation that are mainly or exclusively expressed during cell division, such as kinases, motor proteins and multiprotein complexes. Such small molecules are now in preclinical studies and clinical trials, and many are products or derivatives from natural sources. In this review, we focused on the most promising targets for the development of antimitotics and discussed the advantages and disadvantages of these targets. We also highlighted the novel natural antimitotic agents under investigation by our research group, including combretastatins, withanolides and pterocarpans, which show the potential to circumvent the main issues in antimitotic therapy.

https://doi.org/10.6061/clinics/2018/e813s 3580 downloads

Synthesis and Evaluation of Cytotoxic Effects of Amino-ester Derivatives of Natural α,β-Amyrin Mixture
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Victor, Mauricio M.

; David, Jorge M.

; Santos, Marcelo A. S. dos

; Barreiros, André L. B. S.

; Barreiros, Marizeth L.

; Andrade, Fernanda S.

; Carvalho, Adriana A.

; Luciano, Maria Claudia S.

; Moraes, Manoel O. de

; Barros-Nepomuceno, Francisco W.A.

; Pessoa, Claudia

Journal of the Brazilian Chemical Society

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Nov 2017, Volume 28 Nº 11 Páginas 2155 - 2162

Resumo: En | Texto: En | PDF: En

Natural α,β-amyrins were isolated from endemic Brazilian Esenbeckia grandiflora Mart., and eight synthetic derivatives were obtained by esterification reactions with bromo acetate, followed by amine treatment. The structures of the all compounds were confirmed by 1H and 13C nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR) and high-resolution mass spectrometry (HRMS) data analysis. The derivatives were screened for cytotoxic activity against human tumor cell-lines PC3 (prostate carcinoma), HCT-116 (colon carcinoma) and HL60 (leukemia). HCT-116 and PC3 cell-lines showed weak tumor growth inhibition (range of 13.9-25.4 and 10.3-28.8%, respectively), but the derivatives presented moderate activity against HL60 (range of 13.6-59.0%). Diethyl, aniline, morpholine and imidazole moieties presented higher activities (range of 45.9-59.0%).

https://doi.org/10.21577/0103-5053.20170064 753 downloads

Chemical Profile and Cytotoxic Activity of Leaf Extracts from Senna spp. from Northeast of Brazil
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Silva, Juliana G. A.

; Silva, Alexander A.

; Coutinho, Isabel D.

; Pessoa, Claudia O.

; Cavalheiro, Alberto J.

; Silva, Maria G. V.

Journal of the Brazilian Chemical Society

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Out 2016, Volume 27 Nº 10 Páginas 1872 - 1880

Resumo: En | Texto: En | PDF: En

Methanolic, diethyl ether and n-hexane extracts of leaves of four species of Senna (S. gardneri, S. macranthera, S. splendida and S. trachypus) were analyzed by gas chromatography coupled to mass spectrometry (GC-MS). Using linear retention indices and mass spectral data, 34 compounds were identified, including fatty acids, flavonoids, terpenoids and steroids that were not reported previously for these species. Additionally, the cytotoxicity of the extracts against different tumor cell lines was determined. The cytotoxicity was then correlated with the chemical composition of the extracts by partial least squares-discriminant analysis (PLS-DA). The n-hexane extract of S. gardneri and the ethyl ether extract of S. splendida were the most active against human colon (59.75 and 31.37%, respectively) and human glioblastoma (52.85 and 48.28%, respectively) cell lines.

https://doi.org/10.5935/0103-5053.20160073 1367 downloads

Are salty liquid food flavorings in vitro antitumor substances?
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CARVALHO, FRANCISCO R.S.

; MOURA, ANTONIO G.

; RODRIGUES, GARDENIA F.

; NUNES, NARCIA M.F.

; LIMA, DAISY J.B.

; PESSOA, CLAUDIA

; COSTA, MARCILIA P.

; FERREIRA, PAULO M.P.

; PERON, ANA PAULA

Anais da Academia Brasileira de Ciências

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Set 2016, Volume 88 Nº 3 Páginas 1419 - 1430

Resumo: En | Texto: En | PDF: En

ABSTRACT The objective of this study was to evaluate the antiproliferative, cytotoxic and genotoxic potential of salty liquid synthetic flavorings of Butter, Cheddar Cheese and Onion. The antiproliferative potential (2.9-1500 µg/mL) was assessed by MTT assay after 72h using the human tumor lines SF-295 (glioblastoma), OVCAR-8 (ovarian), HCT-116 (colon) and HL-60 (promyelocytic leukemia) and primary cultures of murine Sarcoma 180 (S180) and peripheral blood mononuclear cells (PBMC). Allium cepa bulbs were exposed to growing respective doses (1 mL and 2 mL). Only Butter and Cheddar flavorings revealed cytotoxic activity on cancer cells, with IC50 values ranging from 125.4 µg/mL (Cheddar - HCT-116) to 402.6 µg/mL (Butter - OVCAR-8). Butter flavoring was the most cytotoxic on PBMC (136.3 µg/mL) and increased cell division rate in relation to the mitotic index but did not cause cellular aberrations. Onion and Cheddar flavorings reduced the mitotic index after 24h and 48h exposure, but only Onion flavoring resulted in cellular aberrations and mitotic spindle abnormalities, such as anaphase and telophase bridges, micronucleated cells, conchicine-metaphases and amplifications. So, Butter, Onion and/or Cheddar flavorings caused significant changes in the division of meristematic cells of A. cepa and presented cytotoxic action even on decontrolled proliferating human tumor cells.

https://doi.org/10.1590/0001-3765201620150553 1749 downloads

Cytotoxicity and Leishmanicidal Activity of Isoniazid-Derived Hydrazones and 2-Pyrazineformamide Thiosemicarbazones
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Amim, Raquel S.

; Firmino, Gisele S. S.

; Rego, Ana C. P. D.

; Nery, Adriane L.

; Da-Silva, Silvia A. G.

; Souza, Marcus V. N. de

; Pessoa, Claudia

; Resende, Jackson A. L. C.

; Figueroa-Villar, José D.

; Lessa, Josane A.

Journal of the Brazilian Chemical Society

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Abr 2016, Volume 27 Nº 4 Páginas 769 - 777

Resumo: En | Texto: En | PDF: En

The isoniazid-derived hydrazones 2-pyridinecarbaldehyde- (HPCIH), 2-acetylpyridine- (HAPIH), 2-benzoylpyridine- (HBPIH), 2-pyridineformamide- (HPAmIH) and 2-pyrazineformamide- (HPzAmIH) isonicotinoyl hydrazones, as well as the pyrazinamide-derived thiosemicarbazones 2-pyrazineformamide- (HPzAm4DH), N(4)-methyl-2-pyrazineformamide- (HPzAm4M), N(4)-ethyl-2-pyrazineformamide- (HPzAm4E) and N(4)-phenyl-2-pyrazineformamide- (HPzAm4Ph) thiosemicarbazones, were assayed for their action against intracellular amastigote form of Leishmania (Viannia) braziliensis strains and the glioblastoma multiforme (SF-295), colon adenocarcinoma (HCT-116), ovarian cancer (OVCAR-8) and acute myeloid leukemia (HL-60) human tumor cell lines. All compounds exhibited leishmanicidal effects, with concentrations at which 50% of parasites were inhibited (IC50) in the 10.70-18.84 µM range. Moreover, the compounds were up to 30-fold less toxic to macrophages than to the parasites. Pyrazinamide-derived thiosemicarbazones proved to have poor activity against the tumor cell lines at 5 µg mL-1, whereas, in general the isoniazid-derived hydrazones presented good activity, being HAPIH and HBPIH the most potent compounds (IC50 = 0.42-1.5 µM).

https://doi.org/10.5935/0103-5053.20150330 1249 downloads

10.

Biflorin: an o-naphthoquinone of clinical significance
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WISINTAINER, GABRIELLE G.N.S.

; SIMÕES, EVELYNE R.B.

; LEMOS, TELMA L.G.

; MOURA, SIDNEI

; SOUZA, LUCIANA G.S.

; FONSECA, ALUISIO M.

; MORAES, MANOEL ODORICO

; PESSOA, CLAUDIA

; ROESCH-ELY, MARIANA

; HENRIQUES, JOÃO A.P.

Anais da Academia Brasileira de Ciências

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Dez 2014, Volume 86 Nº 4 Páginas 1907 - 1914

Resumo: Pt En | Texto: Pt En | PDF: Pt | PDF: En

A biflorina é uma o-naftoquinona com comprovados efeitos citotóxicos frente a células tumorais além de atividades antimicrobiana, antitumoral e antimutagênica. A biflorina é um composto isolado das raízes da planta Capraria biflora L.(Schrophulariaceae), originária das Antilhas e da América do Sul, que está localizada em zonas temperadas e tropicais. Este composto mostrou uma potente atividade contra microorganismos gram-positivos e bactérias álcool-ácido resistentes. Tem mostrado eficiência em inibir a proliferação celular em linhagens tumorais CEM, HL-60, B16, HCT-8, MCF-7. Recentemente, a linhagem tumoral SK-Br3 foi tratada com biflorina e demonstrou importante efeito citotóxico. Neste artigo, relatamos informações relacionadas com os primeiros estudos de caracterização estrutural, bem como os últimos relatos sobre a atividade biológica desta molécula.

Biflorin is an o-naphthoquinone with proven cytotoxic effects on tumor cells showing antimicrobial, antitumor and antimutagenic activities. Biflorin is an isolated compound taken from the roots of the plantCapraria biflora L. (Schrophulariaceae), indigenous of the West Indies and South America, which is located in temperate or tropical areas. This compound has shown to be strongly active against grampositive and alcohol-acid-resistant bacteria. It has been efficient in inhibiting the proliferation tumor cell lines CEM, HL-60, B16, HCT-8 and MCF-7. Recently, SK-Br3 cell line was treated with biflorin showing important cytotoxic effects. In this article, information related to the first structural characterization studies are presented, as well as the latest reports concerning the biological activity of this molecule.

https://doi.org/10.1590/0001-3765201420140085 2575 downloads

11.

A new approach for the synthesis of 3-substituted cytotoxic nor-β-lapachones
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Cardoso, Mariana F. C.

; Silva, Illana M. C. B. da

; Santos Júnior, Helvécio M. dos

; Rocha, David R.

; Araújo, Ana Jérsia

; Pessoa, Claudia

; Moraes, Manoel O. de

; Lotufo, Letícia V. C.

; Silva, Fernando de C. da

; Santos, Wilson C.

; Ferreira, Vitor F.

Journal of the Brazilian Chemical Society

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Jan 2013, Volume 24 Nº 1 Páginas 12 - 16

Resumo: Pt En | Texto: Pt En | PDF: Pt | PDF: En

Vários estudos têm mostrado o potencial citotóxico de derivados da nor-β-lapachona contra células tumorais. Considerando a nor-β-lapachona um importante protótipo, uma série inédita de nor-β-lapachonas substituídas em C-3 foi sintetizada através de uma nova metodologia sintética envolvendo intermediário sintético 3-hidróxi-nor-β-lapachona para o acoplamento de alguns nucleófilos contendo núcleos derivados de carboidratos ou 2H-pirazóis. Todos os derivados foram avaliados frente a quatro linhagens de células tumorais. Duas das substâncias apresentaram moderada citotoxicidade, enquanto as demais inibiram fortemente todas as linhagens tumorais testadas.

Several studies have demonstrated the cytotoxic potential of nor-β-lapachone derivative against cancer cells. Considering nor-β-lapachone as an important prototype, a set of new 3-substituted nor-β-lapachones was synthesized by a new synthetic route that involves the use of synthetic intermediate generated for coupling with several nucleophiles containing the carbohydrate and 2H-pyrazole substituent moieties. All the compounds were screened against four tumor cell lines. Two of the compounds showed moderate cytotoxicity, while the other compounds strongly inhibit all tested cancer cell lines.

2637 downloads

12.

Trachylobane and kaurane diterpenes from Croton floribundus spreng
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Uchôa, Paula Karina S.

; Silva Jr., José Nunes da

; Silveira, Edilberto Rocha

; Lima, Mary Anne S.

; Braz-Filho, Raimundo

; Costa-Lotufo, Letícia Veras

; Araújo, Ana Jérsia

; Moraes, Manoel Odorico de

; Pessoa, Claudia do Ó

Química Nova

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2013, Volume 36 Nº 6 Páginas 778 - 782

Resumo: En | Texto: En | PDF: En

A new trachylobane diterpene ent-trachyloban-18,19-diol (1) was isolated from root bark of Croton floribundus, along with known diterpenes ent-trachyloban-19-oic acid (2), 15b-hydroxy-ent-trachyloban-19-oic acid (3), ent-trachyloban-19-ol (4), ent-kaur-16-en-19-oic acid (5), ent-kaur-16-ene-6a,19-diol (6) and ent-16a-hydroxykaur-11-en-19-oic acid (7). ent-trachyloban-18,19-diol (1) was submitted to derivatization reactions affording four new compounds (8-11). Cytotoxic activity of diterpenes 1, 3, 4, 7-11 against three human cancer cell lines was evaluated. No compounds showed cytotoxic potential with IC50 values greater than 25 mg/mL. Compound 6 was evaluated against five human cancer cell lines, showing moderate effect against three cancer cell lines, MDA-MB-435, HCT-8 and HCT-116, with IC50 values of 14.32, 13.47 and 12.1 mg/mL, respectively.

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13.

Interpretation of the presence of IgM and IgG antibodies in a rapid test for dengue: analysis of dengue antibody prevalence in Fortaleza City in the 20th year of the epidemic
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Lima, José Rubens Costa

; Rouquayrol, Maria Zélia

; Callado, Maria Roseli Monteiro

; Guedes, Maria Izabel Florindo

; Pessoa, Claudia

Revista da Sociedade Brasileira de Medicina Tropical

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Abr 2012, Volume 45 Nº 2 Páginas 163 - 167

Resumo: Pt En | Texto: Pt En | PDF: Pt | PDF: En

INTRODUÇÃO: O diagnóstico de infecções por dengue e sua diferenciação entre infecções primárias e secundárias são importantes para monitorar a disseminação de epidemias e para identificar riscos de formas graves da doença. A detecção de anticorpos IgM e IgG tem sido o principal mecanismo para o diagnóstico laboratorial. Este estudo visa avaliar a capacidade do teste rápido para dengue para: detectar casos novos da doença, diagnosticar reinfecções e estimar taxas de ataque de epidemias. MÉTODOS: Este trabalho consiste de estudo descritivo, transversal retrospectivo, sobre dengue, que utiliza o banco de dados da Secretaria Municipal de Saúde de Fortaleza. Os resultados de 1.530 amostras testadas entre 2005-2006 foram confrontados com dados de estudos epidemiológicos relativos aos surtos de dengue em 1996, 2003 e 2010. RESULTADOS: o teste foi capaz de confirmar 52% de infecções recentes entre pacientes com suspeitas clínicas de dengue: 40% das infecções foram confirmadas pela banda IgM e 12% de casos extras foram detectados pela banda IgG reagente em amostras IgM nãoreagentes. Resultados IgM reagentes e IgG não-reagentes mostraram que 38% das infecções eram primárias, enquanto resultados IgG reagentes, com ou sem IgM reagente, indicaram que 62% das infecções recentes eram reinfecções. Esta proporção de infecções secundárias permitiu estimar a taxa de ataque como maior ou igual a 62% naquela população amostral. CONCLUSÕES: O teste rápido para dengue apresentou capacidade aumentada para diagnosticar infecções recentes e de caracterizá-las entre infecções primárias e secundárias, permitindo estimar a taxa de ataque mínima para a população amostral de um surto.

INTRODUCTION: The diagnosis of dengue and the differentiation between primary and secondary infections are important for monitoring the spread of the epidemic and identifying the risk of severe forms of the disease. The detection of immunoglobulin (Ig)M and IgG antibodies is the main technique for the laboratory diagnosis of dengue. The present study assessed the application of a rapid test for dengue concerning detection of new cases, reinfection recognition, and estimation of the epidemic attack rate. METHODS: This was a retrospective, cross-sectional, descriptive study on dengue using the Fortaleza Health Municipal Department database. The results from 1,530 tested samples, from 2005-2006, were compared with data from epidemiological studies of dengue outbreaks in 1996, 2003, and 2010. RESULTS: The rapid test confirmed 52% recent infections in the tested patients with clinical suspicion of dengue: 40% detected using IgM and 12% of new cases using IgG in the non-reactive IgM results. The positive IgM plus negative IgG (IgM+ plus IgG-) results showed that 38% of those patients had a recent primary dengue infection, while the positive IgG plus either positive or negative IgM (IgG+ plus IgM+/-) results indicated that 62% had dengue for at least a second time (recent secondary infections). This proportion of reinfections permitted us to estimate the attack rate as >62% of the population sample. CONCLUSIONS: The rapid test for dengue has enhanced our ability to detect new infections and to characterize them into primary and secondary infections, permitting the estimation of the minimal attack rate for a population during an outbreak.

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14.

Evaluating methods for the isolation of marine-derived fungal strains and production of bioactive secondary metabolites
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Kossuga, Miriam H.

; Romminger, Stelamar

; Xavier, Camila

; Milanetto, Marília C.

; Valle, Milene Z. do

; Pimenta, Eli F.

; Morais, Raquel P.

; Carvalho, Erica de

; Mizuno, Carolina M.

; Coradello, Luís Fernando C.

; Barroso, Vinícius de M.

; Vacondio, Bruna

; Javaroti, Darci C. D.

; Seleghim, Mirna H. R.

; Cavalcanti, Bruno C.

; Pessoa, Claudia

; Moraes, Manoel O.

; Lima, Bruna A.

; Gonçalves, Reginaldo

; Bonugli-Santos, Rafaella C.

; Sette, Lara D.

; Berlinck, Roberto G. S.

Revista Brasileira de Farmacognosia

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Abr 2012, Volume 22 Nº 2 Páginas 257 - 267

Resumo: En | Texto: En | PDF: En

In the present investigation we evaluate methods for the isolation and growth of marine-derived fungal strains in artificial media for the production of secondary metabolites. Inoculation of marine macroorganisms fragments in Petri dishes proved to be the most convenient procedure for the isolation of the largest number of strains. Among the growth media used, 3% malt extract showed the best result for strains isolation and growth, and yielded the largest number of strains from marine macroorganisms. The percentage of strains isolated using each of the growth media which yielded cytotoxic and/or antibiotic extracts was in the range of 23-35%, regardless of the growth media used. Further investigation of extracts obtained from different marine-derived fungal strains yielded several bioactive secondary metabolites, among which (E)-4-methoxy-5-(3-methoxybut-1-enyl)-6-methyl-2H-pyran-2-one is a new metabolite isolated from the Penicillium paxilli strain Ma(G)K.

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15.

Folk uses and pharmacological properties of Casearia sylvestris: a medicinal review
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Ferreira, Paulo Michel P.

; Costa-Lotufo, Leticia V.

; Moraes, Manoel O.

; Barros, Francisco W.A.

; Martins, Aline M.A.

; Cavalheiro, Alberto J.

; Bolzani, Vanderlan S.

; Santos, Andre G.

; Pessoa, Claudia

Anais da Academia Brasileira de Ciências

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Dez 2011, Volume 83 Nº 4 Páginas 1373 - 1384

Resumo: Pt En | Texto: Pt En | PDF: Pt | PDF: En

Usos populares e pesquisas científicas têm destacado a importância dos extratos da planta Casearia sylvestris e seu grande potencial bioativo. Neste trabalho, objetiva-se revisar as propriedades farmacológicas de C. sylvestris, enfatizando sua potencialidade antiulcerogênica, antiinflamatória, antiofídica e antitumoral. O extrato etanólico e o óleo essencial das folhas possuem atividade antiulcerogênica promissora, diminuindo o volume gástrico sem alterar o pH estomacal, corroborando sua aplicação contra dores gastrointestinais. Já os extratos aquosos das folhas têm atividade inibitória contra fosfolipase A2 presente em venenos de cobras, atenuando os efeitos lesivos sobre a musculatura esquelética resultantes da inoculação das toxinas. Essa ação antifosfolipásica provavelmente está relacionada ao seu uso como antiinflamatório, sugerindo um bloqueio análogo ao dos fármacos antiinflamatórios não-esteroidais na formação de mediadores oriundos do ácido araquidônico e na ativação da ciclooxigenase. Ensaios de fracionamento bioguiado dos extratos culminaram no isolamento e identificação de inúmeros metabólitos secundários, especialmente os diterpenos clerodânicos casearinas (A-X) e casearvestrinas (AC), compostos que têm surpreendido por sua ação citotóxica e antitumoral. Assim, a planta C. sylvestris apresenta um enorme arsenal farmacológico já mundialmente comprovado por seu vasto uso popular, estimulando pesquisas por novas moléculas e a busca pela compreensão de suas propriedades biológicas.

Folk uses and scientific investigations have highlighted the importance of Casearia sylvestris extracts and their relevant bioactive potential. The aim of this work was to review the pharmacological properties of C. sylvestris, emphasizing its anti-ulcer, anti-inflammatory, anti-ophidian and antitumor potentialities. Ethanolic extracts and essential oil of their leaves have antiulcerogenic activity and reduce gastric volume without altering the stomach pH, which corroborates their consumption on gastrointestinal disorders. Leaf water extracts show phospholipase A2 inhibitory activity that prevents damage effects on the muscular tissue after toxin inoculation. This antiphospholipasic action is probably related to the use as an anti-inflammatory, proposing a pharmacological blockage similar to that obtained with non-steroidal anti-inflammatory drugs on arachidonic acid and cyclooxygenase pathways. Bioguided-assay fractionations lead to the identification of secondary metabolites, especially the clerodane diterpenes casearins (A-X) and casearvestrins (A-C), compounds with a remarkable cytotoxic and antitumor action. Therefore, the C. sylvestris shrub holds a known worldwide pharmacological arsenal by its extensive folk utilization, exciting searches for new molecules and a better comprehension about biological properties.

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