Anticancer and anti-inflammatory activities of a standardized dichloromethane extract from piper umbellatum l. leaves

Despite the advances in anticancer drug discovery field, the worldwide cancer incidence is remarkable, highlighting the need for new therapies focusing on both cancer cell and its microenvironment. The tumor microenvironment offers multiple targets for cancer therapy, including inflammation. Nowadays, almost 75% of the anticancer agents used in chemotherapy are derived from natural products, and plants are an important source of new promising therapies. Continuing our research on Piper umbellatum species, here we describe the anticancer (in vitro antiproliferative activity and in vivo Ehrlich solid tumor model) and anti-inflammatory (carrageenan-induced paw edema and peritonitis models) activities of a standardized dichloromethane extract (SDE) from P. umbellatum leaves, containing 23.9% of 4-nerolidylcatechol. SDE showed in vitro and in vivo antiproliferative activity, reducing Ehrlich solid tumor growth by 38.7 and 52.2% when doses of 200 and 400 mg/kg, respectively, were administered daily by oral route. Daily treatments did not produce signals of toxicity. SDE also reduced paw edema and leukocyte migration on carrageenan-induced inflammation models, suggesting that the anticancer activity of SDE from Piper umbellatum leaves could involve antiproliferative and anti-inflammatory effects. These findings highlight P. umbellatum as a source of compounds against cancer and inflammation2015CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPES133897/2012-5sem informaçã

Synthesis, Dna Binding, And Antiproliferative Activity Of Novel Acridine-thiosemicarbazone Derivatives.

In this work, the acridine nucleus was used as a lead-compound for structural modification by adding different substituted thiosemicarbazide moieties. Eight new (Z)-2-(acridin-9-ylmethylene)-N-phenylhydrazinecarbothioamide derivatives (3a-h) were synthesized, their antiproliferative activities were evaluated, and DNA binding properties were performed with calf thymus DNA (ctDNA) by electronic absorption and fluorescence spectroscopies. Both hyperchromic and hypochromic effects, as well as red or blue shifts were demonstrated by addition of ctDNA to the derivatives. The calculated binding constants ranged from 1.74 × 10(4) to 1.0 × 10(6) M(-1) and quenching constants from -0.2 × 10(4) to 2.18 × 10(4) M(-1) indicating high affinity to ctDNA base pairs. The most efficient compound in binding to ctDNA in vitro was (Z)-2-(acridin-9-ylmethylene)-N- (4-chlorophenyl) hydrazinecarbothioamide (3f), while the most active compound in antiproliferative assay was (Z)-2-(acridin-9-ylmethylene)-N-phenylhydrazinecarbothioamide (3a). There was no correlation between DNA-binding and in vitro antiproliferative activity, but the results suggest that DNA binding can be involved in the biological activity mechanism. This study may guide the choice of the size and shape of the intercalating part of the ligand and the strategic selection of substituents that increase DNA-binding or antiproliferative properties.1613023-1304

Estudo fitoquimico de Poecilanthe parviflora Benth. e Lonchocarpus atropurpureus Benth. (Leguminosae) isolamento, determinação estrutural e atividade biologica

Orientador: Eva Gonçalves MagalhãesDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de QuimicaMestrad

Estudo fitoquimico de algumas especies de Eleocharis R. Br. (Cyperaceae) : isolamento, elucidação estrutural e atividade biologica

Orientador: Eva Gonçalves MagalhãesTese (doutorado) - Universidade Estadual de Campinas, Instituto de QuimicaDoutorad

Antiproliferative effect of synthetic cyclic imides (methylphtalimides, carboxylic acid phtalimides and itaconimides) against human cancer cell lines

This work describes the antiproliferative potential of 14 cyclic imides (methylphtalimides, carboxylic acid phtalimides and itaconimides) against several human cancer cell lines. The antiproliferative effect was evaluated using the sulforhodamine B assay. Although some compounds from methylphtalimide and carboxylic acid phtalimide classes exhibited a selective antiproliferative activity, the itaconimides (11-14) exhibited the best results, especially compound 14, which presented a TGI (concentration that produces total growth inhibition) value of 0.0043 mu M against glioma (U251), being inactive against the non-tumor cell line (HaCat). Absorption, distribution, metabolism and excretion in silico evaluations suggest that these compounds are promising candidates7111-12423427CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFundo de Apoio a Manutencao e ao Desenvolvimento da Educacao Superior - FUMDES (State of Santa Catarina); RIBECANCER/CYTED/CNPq Networ

A comprehensive characterization of polyphenols by LC-ESI-QTOF-MS from Melipona quadrifasciata anthidioides geopropolis and their antibacterial, antioxidant and antiproliferative effects

The geopropolis is a unique type of propolis produced by some stingless bee species. This product is known in folk medicine for its pharmacological properties, mainly antimicrobial and antioxidant, but there are few scientific studies that prove these properties. The objective of this study was to evaluate the phenolic composition and the antimicrobial, antioxidant and antiproliferative activities of Melipona quadrifasciata geopropolis. The phenolic characterization of the geopropolis ethanolic extract was evaluated by LC-ESI-QTOF-MS. The antimicrobial activity was carried out against Gram-positive (including multiresistant microorganisms), negative and yeast. The synergistic effect was evaluated in association with Sulfamethoxazole + Trimethoprim. DPPH, ABTS, FRAP, ORAC and HPLC on-line were used to evaluate the antioxidant activity. Antiproliferative activity was assessed by the sulforhodamine B assay. Flavonoids and phenolic acids were identified in the extract, which showed promising antimicrobial activity, partially synergistic effect and antioxidant activityCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPE

Chemical composition and antiproliferative activity of croton campestris a.st.-hil. essential oil

Herein, the antiproliferative potential of the essential oil obtained from fresh leaves of Croton campestris against human tumour cell lines was investigated for the first time. Furthermore, the essential oil obtained by hydrodistillation had the composition determined by gas chromatography-mass spectrometry (GC/MS). Ten major components were identified that comprised 91.59% of the total content, with 23.8% consisting of (Z)-caryophyllene and 16.08% consisting of gamma-elemene as main components. The cytotoxic activity was observed mainly for breast (MCF-7) and colon (HT-29) human tumour cell lines, with GI(50) (50% growth inhibition) concentration of 8.61 and 9.94 mu g/mL, respectively. The results of this study showed that the essential oil obtained from Croton campestris A.St.-Hil. represents a potential source for the search of new antitumour agents334580FAPESP – Fundação de Amparo à Pesquisa Do Estado De São Paulo2011/22457-

Enzymatic Hydrolysis of Rutin: Evaluation of Kinetic Parameters and Anti-Proliferative, Mutagenic and Anti-Mutagenic Effects

The bioavailability of glucoside flavonoids is influenced by the nature of the sugar, glucosides being absorbed faster than rhamnoglucosides, for example. One strategy to enhance the bioavailability is enzymatic hydrolysis. In this study, some kinetic parameters of hesperidinase-mediated hydrolysis of rutin were evaluated using an UHPLC/QTOF-MSE analysis of the products of a bioconversion reaction. The resulting hydrolyzed rutins (after 4, 8 and 12 h of reaction) were submitted to anti-proliferative and Cytokinesis-Block Micronucleus (CBMN) assays in CHO-K1 cells. In the hesperidinase-mediated hydrolysis, the final concentration of quercetin-3-O-glucoside (Q3G) was directly proportional to the rutin concentration and inversely proportional to the reaction time. At an anti-proliferative concentration (2.5 μg/mL), hydrolyzed rutin derivatives did not show a mutagenic effect, except for the sample with a higher content of Q3G (after 4 h of the enzymatic hydrolysis of rutin). Moreover, the higher Q3G content in hydrolyzed rutin protected the CHO-K1 cells 92% of the time against methyl methanesulfonate-induced mutagenic damage. These results suggested that the anti-mutagenic effect of hydrolyzed rutin might be related to antioxidant and cell death induction. Presenting a good lipophilicity/hydrophilicity ratio, together with antioxidant and anti-mutagenic activities, the hesperidinase-mediated hydrolyzed rutin seemed to be a promisor raw material for the development of food supplements