Semisynthesis, in silico study and in vitro antibacterial evaluation of fucosterol derivatives.

Thirteen fucosterol derivatives were prepared by structural modification at the hydroxyl group in C-3 and catalytic hydrogenation at the carbon-carbon double bond in C-5(6) and C-24(28). The structures of all compounds were established based on their spectral data (IR, MS, and NMR). Fucosterol (1) and its derivatives (2-12, and a mixture of 13a and 13b) were evaluated for their in vitro antibacterial activity against Klebsiella pneumoniae (ATCC 10031), Escherichia coli (ATCC 10536), Pseudomonas aeruginosa (ATCC 15442), Streptococcus mutans (ATCC 0046) and Staphylococcus aureus using the microdilution method. Among them, 1, 8, 9, 10, and a mixture of 13a and 13b exhibited the best antibacterial activity. The derivative 7 was inactive against all bacterial strains evaluated (MIC ≥ 2.327 mM). In addition, the investigation of binding interactions of more active compounds (1, 8, 9, 10, and mixture of 13a and 13b) to appropriate proteins was performed using molecular docking. This paper registers for the first time the in silico studies on the antibacterial activity of compounds 1, 8, 9, 10, and mixture of 13a/13b, and the spectral data of compounds 4, 6, and 7.

Starch-based magnetic nanocomposite for targeted delivery of hydrophilic bioactives as anticancer strategy.

Magnetic nanocomposites were synthesized for the targeted delivery of hydrophilic bioactives through guidance generated by a magnetic field. Superparamagnetic iron oxide nanoparticles (SPIONs) were used to generate hydroxyethyl starch magnetic nanocapsules (HES MNCs). This synthesis allowed the co-encapsulation of oncocalyxone A (onco A) and surface-modified magnetite nanoparticles (Fe3O4@citrate) into the same nanostructure. The synthesized nanocapsules exhibited a core-shell morphology, with an average diameter of 143 nm. This nanocomposite showed potential anticancer activity (IC50) against four human tumor cell lines: glioblastoma SNB-19 (1.010 µgmL-1), colon carcinoma HCT-116 (2.675 µgmL-1), prostate PC3 (4.868 µgmL-1), and leukemia HL-60 (2.166 µgmL-1). Additionally, in vivo toxicity and locomotor activity were evaluated in a zebrafish (Danio rerio) model. The nanocomposite exhibited in vitro cytotoxicity, prolonged drug release profile and also responded to an applied magnetic field, representing a versatile compound with perspectives for highest concentration of different hydrophilic bioactives in a target tissue through magnetic vectorization.

Insecticidal Compound from Himatanthus drasticus Latex against Cowpea Infestation by Callosobruchus maculatus (Coleoptera: Chrysomelidae).

Vigna unguiculata is an important source of proteins and energy for humans and animals. However, postharvest losses caused by Callosobruchus maculatus can reach from 20 to 100% of stored seeds. In this study, the insecticide potential of compounds extracted from Himatanthus drasticus latex was assessed. The latex was extracted with ethanol (70%) and then partitioned through sequential use of hexane and chloroform. These fractions were investigated by chromatography to determine their chemical composition. Plumieride, identified in a hydroalcoholic subfraction, was tested for insecticidal activity against C. maculatus. The ethanolic fraction (LC50 = 0.109; LC90 = 0.106%) and the plumieride (LC50 = 0.166; LC90 = 0.167%) were lethal to larvae. Plumieride (0.25%) delayed larval development, and mortality reached 100%. Its inhibitory action on intestinal α-amylase from larvae was higher (89.12%) than that of acarbose (63.82%). Plumieride (0.1%) inhibited the enzyme α-amylase in vivo in the larval intestine. This result was confirmed by a zymogram test performed by SDS-PAGE when the enzyme electrophoresed on gel copolymerized with starch. When spread on seeds, the hydroalcoholic fraction (1.0%) reduced infestation. The loss of seed mass was 5.26% compared to the control (44.97%). The results confirm the effect of latex compounds in protecting stored seeds against weevil infestation.

Chemical profiling of secondary metabolites from Himatanthus drasticus (Mart.) Plumel latex with inhibitory action against the enzymes α-amylase and α-glucosidase: In vitro and in silico assays.

ETHNOPHARMACOLOGICAL RELEVANCE: Himatanthus drasticus is an important medicinal plant whose latex is traditionally used in Northeast Brazil to treat various diseases, including diabetes. The use of α-amylase and α-glucosidase inhibitors can be an effective strategy to modulate levels of postprandial hyperglycemia via control of starch metabolism. AIMS OF THE STUDY: This study aimed to verify if H. drasticus latex has inhibitory activity against enzymes linked to type 2 diabetes, besides chemically characterizing the metabolites responsible for such activities. In addition, in silico analysis was performed to support the traditional claim of possible antidiabetic activity of this latex. MATERIALS AND METHODS: Latex from H. drasticus stems was sequentially partitioned with n-hexane (FHDH), CHCl3 (FHDC) and EtOH (FHDHA). Wash extraction of the FHDHA fraction was performed to obtain the other extract fractions. The FHDHA was submitted to chromatography in a SPE C18 cartridge using gradient elution with MeOH/H2O to produce five fractions: FHDHA1, FHDHA2, FHDHA3, FHDHA4 and FHDHA5. The FHDHA1 was subjected to semi-preparative reverse phase HPLC. Lineweaver-Burk plots were used to investigate the kinetic parameters of α-amylase and α-glucosidase inhibitory activity. The interactions between plumieride and porcine pancreatic α-amylase and α-glucosidase were analyzed through an in silico molecular docking study. RESULTS: Phytochemical identification of compounds present in the FHDHA fraction of H. drasticus latex was possible by 1H, 13C NMR analysis and mass spectrometry, and the results were compared with the literature. The identified compounds were α-ethyl glucoside, protocatechuic acid, 3-O-caffeoylquinic acid, 15-demethylplumieride acid, 5-O-caffeoylquinic acid, caffeic acid, vanillic acid, plumieride, and catechin. The inhibition results of the fractions tested against α-amylase and α-glucosidase showed inhibitory activities dependent on the increase of fractions and compound concentrations. The IC50 results obtained from FHDHA, FHDHA1 and plumieride fractions against α-amylase were 36.46, 72.61, 33.87 µg/mL respectively. The IC50 of plumieride was the closest to that of acarbose (22.52 µg/mL), a result similar to that obtained for α-glucosidase. The type of inhibition was competitive for both enzymes. CONCLUSIONS: There was strong inhibition of α-amylase and α-glucosidase by FHDHA, FHDHA1 and plumieride, suggesting that these enzymes slow glucose absorption.

Magnetic Hybrid Wax Nanocomposites as Externally Controlled Theranostic Vehicles: High MRI Enhancement and Synergistic Magnetically Assisted Thermo/Chemo Therapy.

To fight against cancer, smarter drugs and drug delivery systems are required both to boost the efficiency of current treatments while reducing deleterious side effects, and combine diagnosis/monitoring with therapy (theranosis) in the search for the final goal of personalized medicine. This work presents the design, preparation, and proof-of-principle validation of a novel hybrid organic-inorganic nanocomposite joining together non-invasive imaging capabilities through magnetic resonance imaging and externally actuated therapeutic properties through a combination of chemo- and thermotherapy. The lipidic matrix of the nanocomposite was composed of carnauba wax, which was simultaneously dual loaded with magnetite nanoparticles and the anticancer drug Oncocalyxone A. Obtained formulations were fully characterized and showed outstanding performances as T2 -contrast agents in magnetic resonance imaging (r2 >800 mm-1 s-1 ), heat generating sources in magnetic hyperthermia (specific absorption rate, SAR>200 W g-1 Fe ), and magnetically responsive drug delivery vehicles. The potential of the designed formulations as theranostic agents was validated in vitro and results indicated a synergistic thermo/chemotherapeutic effect derived from heat generation and controlled drug delivery to cancer growth. Thereby, this external control over the drug delivery profile and the integrated imaging capability open the door to personalized cancer medicine and real-time monitoring of tumor progression.

Potent Cytotoxic Analogs of Amphidinolides from the Atlantic Octocoral Stragulum bicolor.

Amphidinolides are cytotoxic macrolides produced by symbiotic unicellular microalgae of the genus Amphidinium. Here we describe the identification of four related molecules belonging to this macrolide family isolated from the invertebrate Stragulum bicolor. The new molecules, named amphidinolide PX1-PX3 and stragulin A (1⁻4), show an unprecedented carbon skeleton whose complete stereochemistry has been determined by spectroscopic and computational methods. Differences in the structures of these molecules modulate their biological activity in a panel of tumor cell lines, but the opened derivative stragulin (4) shows a very potent and specific cytotoxic activity (IC50 0.18 µM) against the aggressive human melanoma cell A2058.

Withaferin A and Withanolide D Analogues with Dual Heat-Shock-Inducing and Cytotoxic Activities: Semisynthesis and Biological Evaluation.

Withanolides constitute a valuable class of bioactive natural products because some members of the class are known to exhibit cytotoxic activity and also induce a cytoprotective heat-shock response. In order to understand the relationship between their structures and these dual bioactivities of the withanolide scaffold, we obtained 25 analogues of withaferin A (WA) and withanolide D (WD) including 17 new compounds by semisynthesis involving chemical and microbial transformations. Hitherto unknown 16ß-hydroxy analogues of WA and WD were prepared by their reaction with triphenylphosphine/iodine, providing unexpected 5ß-hydroxy-6α-iodo analogues (iodohydrins) followed by microbial biotransformation with Cunninghamella echinulata and base-catalyzed cyclization of the resulting 16ß-hydroxy iodohydrins. Evaluation of these 25 withanolide analogues for their cytotoxicity and heat-shock-inducing activity (HSA) confirmed the known structure-activity relationships for WA-type withanolides and revealed that WD analogues were less active in both assays compared to their corresponding WA analogues. The 5ß,6ß-epoxide moiety of withanolides contributed to their cytotoxicity but not HSA. Introduction of a 16ß-OAc group to 4,27-di- O-acetyl-WA enhanced cytotoxicity and decreased HSA, whereas introduction of the same group to 4- O-acetyl-WD decreased both activities.

Endophytic fungus Pseudofusicoccum stromaticum produces cyclopeptides and plant-related bioactive rotenoids.

In the present study, we integrated liquid chromatography high-resolution mass spectrometry (LC-HRMS) and high-throughput DNA sequencing for prospecting cytotoxic specialized metabolites from Pseudofusicoccum stromaticum, an endophytic fungus associated to the medicinal plant Myracrodruon urundeuva. LC-HRMS profiling allowed identifying putatively eleven compounds in the ethyl acetate extract from P. stromaticum broth. Additionally, a chemical fractionation guided by cytotoxicity combined with spectrometric analysis resulted in the isolation of three compounds: the cyclopeptide cyclo-l-Phe-d-Leu-l-Leu-l-Leu-l-lle along with the known rotenoids rotenolone and tephrosin. MTT assay showed that tephrosin (IC50 0.51 µg mL-1) has strong cytotoxic effect and may be pointed out as the compound responsible for the antiproliferative activity of P. stromaticum. Next Generation Sequencing (NGS) and genome mining of P. stromaticum draft genome revealed 56 contigs codifying specialized metabolites biosynthesis-related enzymes. Nearly half of such genes (44.6%) could be mapped to orphan Biosynthetic Gene Clusters (BGCs) of related plant pathogens belonging to family Botryosphaeriaceae. Also, screening for rotenoids biosynthetic enzymes led to characterization of a putative chalcone isomerase-like (CHI-like) protein. This is the first report of rotenoids biosynthesized by a fungus, unveiling a unique ability of P. stromaticum.

Prospecting Anticancer Compounds in Actinomycetes Recovered from the Sediments of Saint Peter and Saint Paul's Archipelago, Brazil.

Saint Peter and Saint Paul's Archipelago is a collection of 15 islets and rocks remotely located in the equatorial Atlantic Ocean. In this particular site, the present project intended to assess the biodiversity and biotechnological potential of bacteria from the actinomycete group. This study presents the first results of this assessment. From 21 sediment samples, 268 strains were isolated and codified as BRA followed by three numbers. Of those, 94 strains were grown in liquid media and submitted to chemical extractions with AcOEt (A), BuOH (B), and MeOH (M). A total of 224 extracts were screened for their cytotoxic activity and 41 were significantly active against HCT-116 cancer cells. The obtained IC50 values ranged from 0.04 to 31.55 µg/ml. The HR-LC/MS dereplication analysis of the active extracts showed the occurrence of several known anticancer compounds. Individual compounds, identified using HR-MS combined with analysis of the AntiMarin database, included saliniketals A and B, piericidins A and C and glucopiericidin A, staurosporine, N-methylstaurosporine, hydroxydimethyl-staurosporine and N-carbamoylstaurosporine, salinisporamycin A, and rifamycins S and B. BRA-199, identified as Streptomyces sp., was submitted to bioassay-guided fractionation, leading to isolation of the bioactive piericidins A and C, glucopiericidin, and three known diketopiperazines, cyclo(l-Phe-trans-4-OH-l-Pro), cyclo(l-Phe-l-Pro), and cyclo(l-Trp-l-Pro).

Dinoflagellate-Related Amphidinolides from the Brazilian Octocoral Stragulum bicolor.

Benthic cnidarians are colonial marine animals that host a rich population of associated and symbiotic microorganisms. In a recent paper we described for the first time the isolation of amphidinolide P (1) from the Brazilian octocoral Stragulum bicolor. Amphidinolides and similar compounds had been previously reported only from dinoflagellates of the genus Amphidinium; thus the presence of 1 in the invertebrate opens intriguing questions on the role and occurrence of these molecules in marine ecosystems. Here we report the identification of four further amphidinolides from the same soft coral, including the known amphidinolide T1 (2) and the new analogues here named amphidinolides C4 (3), B8 (4), and B9 (5). The chemical structures have been elucidated mainly by extensive study of spectroscopic data. Cytotoxic activities of 3 and 4 were evaluated against the colon adenocarcinoma cell line HCT-116.

Amphidinolide P from the Brazilian octocoral Stragulum bicolor

Abstract Dinoflagellates are an important source of unique bioactive secondary metabolites. Symbiotic species, commonly named zooxanthellae, transfer most of their photosynthetically fixed carbon to their host. The mutualistic relationship provides the organic metabolites used for energy production but there are very few reports of the role of the dinoflagellates in the production of secondary metabolites in the symbiotic association. Corals and other related cnidarians are the most well-known animals containing symbiotic dinoflagellates. In the present paper we describe the isolation of amphidinolide P (1) from the octocoral Stragulum bicolor and its prey, the nudibranch Marionia limceana, collected off the coasts of Fortaleza (Ceará, Brazil). The coral extracts also contained 3-O-methyl derivative (2) of amphidinolide P, together with minor compounds still under investigation. Amphidinolides have been so far reported only in laboratory cultures of Amphidinium sp., thus compounds 1 and 2 represents the first identification of these polyketides in invertebrates. The finding proves the possibility to isolate amphidinolides from a natural symbiosis, enabling further biological and biotechnological studies.

Identification of pyrroloformamide as a cytokinesis modulator.

Discovered in the late 1940s, the pyrrolinonodithioles represent a family of potent disulfide-containing natural products. Although they are understood in a synthetic and biosynthetic context, the biological role of these materials remains unresolved. To date, their activity has been suggested to arise through regulating RNA metabolism, and more recently they have been suggested to function as backup thiols for detoxification. Using materials identified through a natural products program, we now identify the biological function of one member of this family, pyrroloformamide, as an antimitotic agent acting, in part, by disrupting cytokinesis.

Magnetic nanosystem for cancer therapy using oncocalyxone a, an antitomour secondary metabolite isolated from a Brazilian plant.

This paper describes the investigation and development of a novel magnetic drug delivery nanosystem (labeled as MO-20) for cancer therapy. The drug employed was oncocalyxone A (onco A), which was isolated from Auxemma oncocalyx, an endemic Brazilian plant. It has a series of pharmacological properties: antioxidant, cytotoxic, analgesic, anti-inflammatory, antitumor and antiplatelet. Onco A was associated with magnetite nanoparticles in order to obtain magnetic properties. The components of MO-20 were characterized by XRD, FTIR, TGA, TEM and Magnetization curves. The MO-20 presented a size of about 30 nm and globular morphology. In addition, drug releasing experiments were performed, where it was observed the presence of the anomalous transport. The results found in this work showed the potential of onco A for future applications of the MO-20 as a new magnetic drug release nanosystem for cancer treatment.

Studies on the secondary metabolites of a Pseudoalteromonas sp. isolated from sediments collected at the northeastern coast of Brazil.

Continuing search for anticancer compounds from the marine environment, we have studied microorganisms that inhabit intertidal sediments of the northeastern Brazilian coast. Of the 32 strains isolated, 13 were selected for biological evaluation of their crude extracts. The acetate extract obtained from a Gram-negative bacterium was strongly active against cancer cell lines with IC(50) values that ranged from 0.04 (HL60 leukemia cells) to 0.26 µg/ml (MDA MB-435 melanoma cells). The bacterium was identified as a Pseudoalteromonas sp. based on 16S rRNA gene sequencing. A bioassay-guided fractionation of the active extract led to the isolation of prodigiosin, a well-known tripyrrole red pigment with immunosuppressive and anticancer activities. Further experiments with ErbB-2 overexpressing cell lines, including HB4a-C3.6 (moderate overexpression), HB4a-C5.2 (high overexpression), and the parental HB4a cell line, were performed. Prodigiosin was moderately active toward HB4a cells with an IC(50) of 4.6 µg/ml, while it was 115 and 18 times more active toward HB4a-C3.6 cells (IC(50) of 0.04 µg/ml) and HB4a-C5.2 (IC(50) of 0.26 µg/ml) cells, respectively. These data suggest that, in spite of its previously described apoptosis-inducing properties, prodigiosin can selectively recognize cells overexpressing ErbB-2, which could be highly appealing in human breast cancer therapy.

Anthracyclinones from Micromonospora sp.

Four new anthracyclinones, 4,6,11-trihydroxy-9-propyltetracene-5,12-dione (1), 1-methoxy-9-propyltetracene-6,11-dione (2), 7,8,9,10-tetrahydro-9-hydroxy-1-methoxy-9-propyltetracene-6,11-dione (3), and 10ß-carbomethoxy-7,8,9,10-tetrahydro-4,6,7α,9α,11-pentahydroxy-9-propyltetracene-5,12-dione (4), were isolated from a strain of Micromonospora sp. associated with the tunicate Eudistoma vannamei. All structures were established by 1D and 2D NMR (COSY, HSQC, HMBC, NOESY) and HRESIMS experiments. Compounds 1 and 4 were cytotoxic against the HCT-8 human colon adenocarcinoma cell line, with IC(50) values of 12.7 and 6.2 µM, respectively, while compounds 2 and 3 were inactive.

In vitro and in vivo antiproliferative activity of Calotropis procera stem extracts.

The cytotoxic potential of stem organic extracts from Calotropis procera (Asclepiadaceae) was firstly evaluated against cancer cell lines by MTT assay. Subsequently, samples considered cytotoxic were tested for antimitotic activity on sea urchin egg development and for in vivo antiproliferative activity in mice bearing Sarcoma 180 tumor. Among the five extracts (hexane, dichloromethane, ethyl acetate, acetone and methanol), ethyl acetate and acetone extracts displayed higher cytotoxic potential against tumor cells, with IC50 ranging from 0.8 to 4.4 microg/mL, while methanolic extract was weakly cytotoxic. Cytotoxic extracts also exhibited cell division inhibition capacity by antimitotic assay, revealing IC50 values lower than 5 microg/mL. In the in vivo antitumor assessments, ethyl acetate- and acetone-treated animals showed tumor growth inhibition ratios of 64.3 and 53.1%, respectively, with reversible toxic effects on liver and kidneys. Further studies are in progress in order to identify C. procera cytotoxic compound(s) and to understand the mechanism of action responsible for this tumor-decreasing potential.

In vitro and in vivo antiproliferative activity of Calotropis procera stem extracts

The cytotoxic potential of stem organic extracts from Calotropis procera (Asclepiadaceae) was firstly evaluated against cancer cell lines by MTT assay. Subsequently, samples considered cytotoxic were tested for antimitotic activity on sea urchin egg development and for in vivo antiproliferative activity in mice bearing Sarcoma 180 tumor. Among the five extracts (hexane, dichloromethane, ethyl acetate, acetone and methanol), ethyl acetate and acetone extracts displayed higher cytotoxic potential against tumor cells, with IC50 ranging from 0.8 to 4.4 μg/mL, while methanolic extract was weakly cytotoxic. Cytotoxic extracts also exhibited cell division inhibition capacity by antimitotic assay, revealing IC50 values lower than 5 μg/mL. In the in vivo antitumor assessments, ethyl acetate- and acetone-treated animals showed tumor growth inhibition ratios of 64.3 and 53.1 percent, respectively, with reversible toxic effects on liver and kidneys. Further studies are in progress in order to identify C. procera cytotoxic compound(s) and to understand the mechanism of action responsible for this tumor-decreasing potential.

O potencial citotóxico de extratos orgânicos do caule de Calotropis procera (Asclepiadaceae) foi primeiramente avaliado frente a linhagens de células tumorais através do ensaio de MTT. Aquelas amostras consideradas citotóxicas foram sub-sequentemente testadas para atividade antimitótica sobre o desenvolvimento de ovos de ouriço-do-mar e para atividade antiproliferativa in vivo em camundongos transplantados com tumor Sarcoma 180. Dentre os cinco extratos estudados (hexano, diclorometano, acetato de etila, acetona e metanol), os extratos acetato de etila e acetona mostraram maior potencial citotóxico contra células tumorais, com CI50 variando de 0,8 to 4,4 μg/mL, enquanto o extrato metanólico revelou ser fracamente citotóxico. s extratos citotóxicos também exibiram capacidade de inibição da divisão celular com valores de CI50 menores que 5 μg/mL. Nas avaliações antitumorais in vivo, os animais tratados com os extratos acetato de etila e acetona mostraram taxas de inibição do crescimento tumoral de 64,3 e 53,1 por cento, respectivamente, com efeitos tóxicos reversíveis sobre o fígado e os rins.

O oleo essencial de Lippia gracilis Schauer, Verbenaceae, em ratos diabeticos / The essential oil from Lippia gracilis Schauer, Verbenaceae, in diabetic rats

O óleo essencial das folhas de Lippia gracilis Schauer, Verbenaceae, foi examinado por CG e CG-MS. Quinze constituintes foram identificados, onde o carvacrol, p-cimeno e o γ-terpineno foram as substâncias majoritárias. No estudo in vitro, a solução a 5 por cento do óleo de L. gracilis Schauer apresentou atividade antibacteriana para Staphylococcus aureus isolado de úlcera infectada de paciente diabético. O estudo avaliou a atividade antibacteriana da solução a 5 por cento do óleo de L. gracilis Schauer em modelo experimental em diabetes utilizando ratos albinos Wistar machos com membro pélvico infectado com cepa de Staphylococcus aureus. No experimento foram utilizados 28 ratos Wistar distribuídos em quatro grupos (G1-branco, G2-controle negativo, G3-controle positivo, G4-teste) de sete ratos. Quando comparado o grupo G4 com G3, observou-se que a solução a 5 por cento promoveu uma redução nas CFU/mL após 24h da administração do inóculo (S.aureus sem L. gracilis Schauer 10(8) ± 313 versus S.aureus com L. gracilis Schauer 13,28 ± 4,03). Os resultados foram expressos através do cálculo da média±EPM) e análise de variança (ANOVA). A diferença entre a concentração inibitória mínima no estudo in vitro foi determinada pelo teste Turkey (p<0.05). O teste Newman-Keuls com nível de significância (p<0.05) foi utilizado para o cálculo dos resultados obtidos no experimento in vivo. A solução a 5 por cento do óleo essencial de Lippia gracilis Schauer apresentou boa atividade antibacteriana tanto no estudo in vivo como no in vitro.

The essential oil from Lippia gracilis Schauer (Verbenaceae) leaves was examined by GC and GC-MS. Fifteen constituents were identified. Carvacrol, p-cymene and γ-terpinene were found to be the major components. In the in vitro study, 5 percent solution of the Lippia gracilis Schauer oil presented antibacterial activity against Staphylococcus aureus isolated from diabetic patients with infected ulcers. The study evaluated the antibacterial activity of the 5 percent solution of the Lippia gracilis Schauer oil on the experimental model of diabetic adult male albino Wistar rats with leaft pelvic limb infected by Staphylococcus aureus strain. In this experiment, 28 diabetic Wistar rats were used, randomly distributed in four different groups of seven rats, (G1-white; G2-negative control; G3-positive control and G4-test). When comparing group G4 with G3, it was observed that the 5 percent solution presented a reduced CFU/mL level showing the antibacterial effect of the oil 24 hours after the administration of the inoculum (S .aureus without Lippia gracilis Schauer 108 ±313 versus S.aureus with Lippia gracilis Schauer 13.28±4.03). The results were expressed as mean±S.E.M. One-way analysis of the variance (ANOVA) was used. The differences between the minimum inhibitory concentration in vitro test were determined by the Tukey test (p<0.05). The Newman-Keuls test with level of significance (p<0.05) was used to measure the results in vivo. The findings have shown that 5 percent solution of the Lippia gracilis Schauer oil presented antibacterial activity in vitro and in vivo.

Oxidative stress induction by (+)-cordiaquinone J triggers both mitochondria-dependent apoptosis and necrosis in leukemia cells.

(+)-Cordiaquinone J is a 1,4-naphthoquinone isolated from the roots of Cordia leucocephala that has antifungal and larvicidal effects. However, the cytotoxic effects of (+)-cordiaquinone J have never being explored. In the present study, the effect of (+)-cordiaquinone J on tumor cells viability was investigated, showing IC(50) values in the range of 2.7-6.6muM in HL-60 and SF-295 cells, respectively. Studies performed in HL-60 leukemia cells indicated that (+)-cordiaquinone J (1.5 and 3.0muM) reduces cell viability and 5-bromo-2-deoxyuridine incorporation after 24h of incubation. (+)-Cordiaquinone J showed rapid induction of apoptosis, as indicated by phosphatidylserine externalization, caspase activation, DNA fragmentation, morphologic changes, and rapid induction of necrosis, as indicated by the loss of membrane integrity and morphologic changes. (+)-Cordiaquinone J altered the redox potential of cells by inducing the depletion of reduced GSH intracellular content, the generation of reactive oxygen species and the loss of mitochondrial membrane potential. However, pre-treatment of cells with N-acetyl-l-cysteine abolished most of the observed effects related to (+)-cordiaquinone J treatment, including those involving apoptosis and necrosis induction.

Nematicidal and larvicidal activities of the essential oils from aerial parts of Pectis oligocephala and Pectis apodocephala Baker.

The chemical composition of the essential oils from aerial parts of Pectis apodocephala and Pectis oligocephala were analyzed by GC-MS. The essential oils of these species were predominantly constituted by monoterpenes. Geranial (42.9-44.5%), neral (32.2-34.2%) and alpha-pinene (10.7-11.4%) were the main constituents in the oil of P. apodocephala, while p-cymene (50.3-70.9%) and thymol (24.4-44.7%), were the prevalent compounds in the oil of P. oligocephala. The essential oils were tested against the root knot nematode Meloidogyne incognita and Aedes aegypti larvae survival. The results obtained show that both essential oils exhibited significant activity and could be considered as potent natural namaticidal and larvicidal agents.