The pharmacological assay as a tool to medicinal plants domestication

In Brazil studies with native medicinal plants are usually performed using non-domesticated plants and as a result the genetic variability of wild species could express different levels of active principles changing their therapeutic effect. Based on that, the aim of this study was to demonstrate that extract of different half- sib families Cordia verbenacea (DC), widely used as medicinal plant in Brazil, have different efficacy in the Total Growth Inhibition (TGI) of 5 different human tumor cell lines. Data were statistically analyzed using ANOVA follow by Tuckey test and a heritability estimation of the plant families was performed. The results showed that TGI are different for each plant family according with each human tumor cell line. For instance, extracts obtained from families 3,11 and 12 were more effective to inhibit the U-251 and Ht-29 cell lines compared to the other families, while extracts obtained from the family 32 was more effective against thethe PC-3 line. The heritability coefficient indicated that plant population selection could promote a genetic improvement related to its active principle and their pharmacological effect and could provide the identification of the best families according to their pharmacological efficacy. In conclusion, this study suggests that the domestication of a wild medicinal plant should be better monitored by its pharmacological effect

Seven-membered Rings Through Metal-free Rearrangement Mediated By Hypervalent Iodine.

A versatile and metal-free approach for the synthesis of carbocycles and of heterocycles bearing seven- and eight-membered rings is described. The strategy is based on ring expansion of 1-vinylcycloalkanols (or the corresponding silyl or methyl ether) mediated by the hypervalent iodine reagent HTIB (PhI(OH)OTs). Reaction conditions can be easily adjusted to give ring expansion products bearing different functional groups. A route to medium-ring lactones was also developed.201475-9

Antimicrobial and antiproliferative potential of Anadenanthera colubrina (vell.) Brenan

The aim of the present study was to perform an in vitro analysis of the antimicrobial and antiproliferative potential of an extract from Anadenanthera colubrina (Vell.) Brenan (angico) and chemically characterize the crude extract. Antimicrobial action was evaluated based on the minimum inhibitory concentration (MIC), minimum bactericidal/fungicidal concentration, and the inhibition of formation to oral biofilm. Cell morphology was determined through scanning electron microscopy (SEM). Six strains of tumor cells were used for the determination of antiproliferative potential. The extract demonstrated strong antifungal activity against Candida albicans ATCC 18804 (MIC = 0.031 mg/mL), with similar activity found regarding the ethyl acetate fraction. The extract and active fraction also demonstrated the capacity to inhibit the formation of Candida albicans to oral biofilm after 48 hours, with median values equal to or greater than the control group, but the difference did not achieve statistical significance (P > 0.05). SEM revealed alterations in the cell morphology of the yeast. Regarding antiproliferative activity, the extract demonstrated cytostatic potential in all strains tested. The present findings suggest strong antifungal potential for Anadenanthera colubrina (Vell.) Brenan as well as a tendency toward diminishing the growth of human tumor cells.The aim of the present study was to perform an in vitro analysis of the antimicrobial and antiproliferative potential of an extract from Anadenanthera colubrina (Vell.) Brenan (angico) and chemically characterize the crude extract. Antimicrobial action was evaluated based on the minimum inhibitory concentration (MIC), minimum bactericidal/fungicidal concentration, and the inhibition of formation to oral biofilm. Cell morphology was determined through scanning electron microscopy (SEM). Six strains of tumor cells were used for the determination of antiproliferative potential. The extract demonstrated strong antifungal activity against Candida albicans ATCC 18804 ( mg/mL), with similar activity found regarding the ethyl acetate fraction. The extract and active fraction also demonstrated the capacity to inhibit the formation of Candida albicans to oral biofilm after 48 hours, with median values equal to or greater than the control group, but the difference did not achieve statistical significance . SEM revealed alterations in the cell morphology of the yeast. Regarding antiproliferative activity, the extract demonstrated cytostatic potential in all strains tested. The present findings suggest strong antifungal potential for Anadenanthera colubrina (Vell.) Brenan as well as a tendency toward diminishing the growth of human tumor cells201

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

Antimicrobial Activity of Essential Oils against Streptococcus mutans and their Antiproliferative Effects

This study aimed to evaluate the activity of essential oils (EOs) against Streptococcus mutans biofilm by chemically characterizing their fractions responsible for biological and antiproliferative activity. Twenty EO were obtained by hydrodistillation and submitted to the antimicrobial assay (minimum inhibitory (MIC) and bactericidal (MBC) concentrations) against S. mutans UA159. Thin-layer chromatography and gas chromatography/mass spectrometry were used for phytochemical analyses. EOs were selected according to predetermined criteria and fractionated using dry column; the resulting fractions were assessed by MIC and MBC, selected as active fractions, and evaluated against S. mutans biofilm. Biofilms formed were examined using scanning electron microscopy. Selected EOs and their selected active fractions were evaluated for their antiproliferative activity against keratinocytes and seven human tumor cell lines. MIC and MBC values obtained for EO and their active fractions showed strong antimicrobial activity. Chemical analyses mainly showed the presence of terpenes. The selected active fractions inhibited S. mutans biofilm formation (P < 0.05) did not affect glycolytic pH drop and were inactive against keratinocytes, normal cell line. In conclusion, EO showed activity at low concentrations, and their selected active fractions were also effective against biofilm formed by S. mutans and human tumor cell lines.Sao Paulo Research Foundation (FAPESP) [2009/12353-0, 2011/14757-0]Sao Paulo Research Foundation (FAPESP)National Council for Scientific and Technological Development (CNPq)National Council for Scientific and Technological Development (CNPq) [308644/2011-5

Purification, characterization and antiproliferative activity of l-asparaginase from Aspergillus oryzae CCT 3940 with no glutaminase activity

Objective: To explore the anti-proliferative activity of purified l-asparaginase from Aspergillus oryzae CCT 3940 (A. oryzae). Methods: l-asparaginase was produced by submerged fermentation and purified to electrophoresis homogeneity by ionic exchanged chromatography in a fast protein liquid chromatographic system. The purified enzyme was characterized and used for the antiproliferative assay against nine tumor cell lines and one non-tumor cell line. Results: The free glutaminase l-asparaginase was purified 28.6 fold. l-asparaginase showed high stability under physiological condition, remaining stable in the pH range 7.0–8.0 after 1 h incubation at temperature range 30–45 °C. The Km and Vmax values of purified l-asparaginase were estimated as 0.66 mmol/L and 313 IU/mL, respectively. The purified enzyme could inhibit the growth of a broad range of human tumor cell lines at the concentrations studied. Also, the enzyme from A. oryzae CCT 3940 could inhibit tumor growth of leukemia cell line (K562) with a total growth inhibition value of (3.2 ± 2.5) IU/mL and did not inhibit the non-carcinogenic human cell line growth at the concentrations studied. Conclusions: The sensitivity of the cells lines to purified l-asparaginase from A. oryzae CCT 3940 appeared to be concentration dependent affording a more significant decrease in cell growth than that observed for the commercial l-asparaginase from Escherichia coli. The l-asparaginase from A. oryzae CCT 3940 has a high potential for pharmaceutical exploitation in the treatment of leukemia

Purification, characterization and antiproliferative activity of l-asparaginase from aspergillus oryzae CCT 3940 with no glutaminase activity

To explore the anti-proliferative activity of purified l-asparaginase from Aspergillus oryzae CCT 3940 (A. oryzae). Methods l-asparaginase was produced by submerged fermentation and purified to electrophoresis homogeneity by ionic exchanged chromatography in a fast protein liquid chromatographic system. The purified enzyme was characterized and used for the antiproliferative assay against nine tumor cell lines and one non-tumor cell line. Results The free glutaminase l-asparaginase was purified 28.6 fold. l-asparaginase showed high stability under physiological condition, remaining stable in the pH range 7.0–8.0 after 1 h incubation at temperature range 30–45 °C. The Km and Vmax values of purified l-asparaginase were estimated as 0.66 mmol/L and 313 IU/mL, respectively. The purified enzyme could inhibit the growth of a broad range of human tumor cell lines at the concentrations studied. Also, the enzyme from A. oryzae CCT 3940 could inhibit tumor growth of leukemia cell line (K562) with a total growth inhibition value of (3.2 ± 2.5) IU/mL and did not inhibit the non-carcinogenic human cell line growth at the concentrations studied. Conclusions The sensitivity of the cells lines to purified l-asparaginase from A. oryzae CCT 3940 appeared to be concentration dependent affording a more significant decrease in cell growth than that observed for the commercial l-asparaginase from Escherichia coli. The l-asparaginase from A. oryzae CCT 3940 has a high potential for pharmaceutical exploitation in the treatment of leukemia69785794FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP2012/24046-

Supercritical carbon dioxide extraction of compounds from Schinus terebinthifolius Raddi fruits: Effects of operating conditions on global yield, volatile compounds, and antiproliferative activity against human tumor cell lines

Schinus terebinthifolius Raddi is a South American plant with medicinal properties. We report the extraction of compounds from S. terebinthifolius fruits using supercritical CO2 (scCO2), with emphasis on the effects of scCO2 pressure (100–300 bar) and temperature (40–60 °C) on global yield, volatile compounds, and antiproliferative activity against nine human tumor cell lines. Supercritical extracts obtained at 50–60 °C, independently of pressure, showed potent activity against kidney cancer with total growth inhibition <3.9 μg/mL. Furthermore, extracts obtained at 200 bar and 50 °C showed potent activity against multidrug-resistant ovarian, prostate, and ovarian tumor cell lines, and glioma. Gas chromatography-mass spectrometry revealed the following volatile compounds: δ-3-carene, α-phellandrene, limonene, germacrene D, and caryophyllene. The results suggest that sesquiterpenes may be the metabolites responsible for the antiproliferative activity. However, future work involving fractionation of the extracts might shed light on the chemical compounds responsible for each antiproliferative activity1301016CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQsem informaçã

Anti-Estrogenic Activity of Guajadial Fraction, from Guava Leaves (Psidium guajava L.)

The research of natural products has allowed for the discovery of biologically relevant compounds inspired by plant secondary metabolites, which contributes to the development of many chemotherapeutic drugs used in cancer treatment. Psidium guajava leaves present a diverse phytochemical composition including flavonoids, phenolics, meroterpenoids, and triterpenes as the major bioactive constituents. Guajadial, a caryophyllene-based meroterpenoid, has been studied for potential anticancer effects tested in tumor cells and animal experimental models. Moreover, guajadial has been reported to have a mechanism of action similar to tamoxifen, suggesting this compound as a promisor phytoestrogen-based therapeutic agent. Herein, the anti-estrogenic action and anti-proliferative activity of guajadial is reported. The enriched guajadial fraction was obtained by sequential chromatographic techniques from the crude P. guajava dichloromethane extract showing promising anti-proliferative activity in vitro with selectivity for human breast cancer cell lines MCF-7 and MCF-7 BUS (Total Growth Inhibition = 5.59 and 2.27 &micro;g&middot;mL&minus;1, respectively). Furthermore, evaluation of anti-estrogenic activity in vivo was performed demonstrating that guajadial enriched fraction inhibited the proliferative effect of estradiol on the uterus of pre-pubescent rats. These results suggest a relationship between anti-proliferative and anti-estrogenic activity of guajadial, which possibly acts in tumor inhibition through estrogen receptors due to the compounds structural similarity to tamoxifen

Kaurenoic acid from Annona squamosa L. exhibits antiproliferative effect on human tumor cell lines and induces apoptosis in Aspergillus nidulans

Made available in DSpace on 2020-02-17T11:40:57Z (GMT). No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) daniela_granella_gomes_et_all.pdf: 726691 bytes, checksum: e6e3f7c19e3b105914c0d5f2ed57ec31 (MD5) Previous issue date: 2019Universidade Estadual de Maringá. Secretaria de Biologia Comparada. Laboratório de Genética Molecular e do Desenvolvimento. Maringá, PR, Brasil.Universidade Estadual de Maringá. Secretaria de Biologia Comparada. Laboratório de Genética Molecular e do Desenvolvimento. Maringá, PR, Brasil.Universidade Tecnológica Federal do Paraná. Campo Mourão, PR, Brasil.Universidade Estadual de Campinas. Faculdade de Ciências Farmacêuticas. Campinas, SP, Brasil.Universidade Estadual de Campinas. Faculdade de Ciências Farmacêuticas. Campinas, SP, Brasil.Universidade Estadual de Campinas. Faculdade de Ciências Farmacêuticas. Campinas, SP, Brasil.Universidade Estadual de Maringá. Centro de Ciências Biológicas. Departamento de Biologia Celular e Genética. Maringá, PR, Brasil.Annona squamosa is a source of bioactive compounds, with several pharmacological activities. However, tests are needed to confirm the safety of these compounds in terms of cytogenotoxic potential and their possible medicinal activity. Thus, the aims of the present study were to isolate kaurenoic acid from sugar apple peel and determine its antiproliferative activity in nine human tumor cell lines and mutagenic activity in germinating Aspergillus nidulans conidia. Chemical extraction resulted in the isolation of kaurenoic acid, a terpene that demonstrated a cytostatic effect at concentrations of 25 and 250 µg mL-1 and antiproliferative at a concentration 250 µg mL-1. The germination test showed that this compound can activate apoptosis, since there was an increase in dead conidia and a decrease in malformed individuals in all treatments. These results indicate its antiproliferative effect and apoptosis activation, representing a useful tool in the development of new chemotherapy drugs