Laurendecumallenes A-B and laurendecumenynes A-B, halogenated nonterpenoid C-15-Acetogenins from the marine red alga Laurencia decumbens

Four new halogenated nonterpenoid C-15-acetogenins, 4:7,6:13-bisepoxy-9,10-diol-1,12-dibromopentadeca-1,2-diene (1, laurendecumallene A), 4:7,6:12-bisepoxy-9,10-diol-1,13-dibromopentadeca-1,2-diene (2, laurendecumallene 13), (3Z)-6:10,7:13-bisepoxy-12-bromo-9-hydroperoxylpentadeca-3-en-1-yne (3, laurendecumenyne A), and (3Z)-6:10,9:13-bisepoxy-12-bromo-7-chloropentadeca-3-en-1-yne (4, laurendecumenyne 13), together with one known halogenated C-15-acetogenin elatenyne (5) were isolated and identified from the organic extract of the marine red alga Laurencia decumbens. Their structures and relative stereochemistry were established by means of spectroscopic analysis including UV, IR, high-resolution electrospray ionization mass spectrometry (HRESIMS), and ID and 2D NMR techniques. All these metabolites were submitted for the cytotoxic assay against tumor cell line A549 (human lung adenocarcinoma), but all of them were found inactive (IC50 > 10 mu g/mL).

Avaliação do potencial leishmanicida e antibacteriano de Annona mucosa (Jacq.) - Annonaceae cultivada in vitro e in vivo

A biodiversidade brasileira abrange plantas de importância medicinal que podem ser utilizadas na formulação de novos fármacos. Contudo, tem sido reduzida em velocidade alarmante, em função de diferentes ações antrópicas. A cultura de tecidos vegetais propicia a conservação e uso do germoplasma permitindo a obtenção de substâncias de importância medicinal. As leishmanioses são consideradas um problema de saúde pública mundial sendo a espécie Leishmania braziliensis de maior importância epidemiológica no Brasil. Recentemente tem-se registrado aumento da resistência à linha de tratamento usual. Do mesmo modo, o uso indiscriminado de antibióticos levou ao aumento de bactérias multirresistentes, que representam sério risco de infecção. A espécie Annona mucosa (Jacq.) possui substâncias, como acetogeninas e alcaloides, que apresentam atividades antiparasitária e antimicrobiana. Nesse sentido, o objetivo do trabalho foi avaliar o potencial leishmanicida e antibacteriano de extratos de A. mucosa de material produzido in vitro e in vivo. Foi proposto um protocolo de germinação in vitro, ainda não reportada para a espécie, com vistas à obtenção de plântulas axênicas. Em meio WPM foram cultivados explantes hipocotiledonares e foliares em meio MS, suplementados com PIC e diferentes concentrações de KIN, BAP ou TDZ. Os calos obtidos foram cultivados em meio líquido de mesma composição para a produção de suspensões celulares. Os materiais foram submetidos à extração metanólica e posterior fracionamento em hexano e diclorometano. Para a avaliação da atividade dos extratos sobre L. braziliensis foi usado o modelo in vitro, com a forma promastigota, e in vivo na forma amastigota, a partir do tratamento de macrófagos peritoneais de camundongos infectados com o parasito. Ambas as formas foram tratadas com os extratos por 96 e 48h, respectivamente. A atividade antimicrobiana foi avaliada por macrodiluição do extrato em Mueller-Hinton, sendo avaliado o crescimento das cepas após 16h de incubação a 48C. A germinação in vitro da espécie foi alcançada em substrato vermiculita estéril umedecido com solução de sais do meio MS, com taxa média de 85%. A maior produção de calos friáveis foi obtida em meios contendo KIN, com potencial uso para cultivo em suspensões celulares. Os extratos do material in situ e in vitro apresentaram atividade leishmanicida, apesar da toxicidade para macrófagos. Culturas de células em suspensão apresentaram potencial leishmanicida in vitro e redução da infecção em macrófagos. Os extratos do material avaliado apresentaram atividade antimicrobiana seletiva, com inibição do crescimento de Streptococcus pyogenes e Bacillus thurigiensis em diferentes concentrações avaliadas. Os métodos biotecnológicos empregados permitiram a obtenção de materiais com propriedades medicinais para as atividades leishmanicida e antibacteriana, assim como o material in vivo, constituindo este estudo o primeiro relato para as atividades propostas em A. mucosa.

冈村凹顶藻中的倍半萜和C15-多聚乙酰类成分研究

凹顶藻属(Laurencia)海藻在分类学上属于红藻门(Rhodophyta)、红藻纲(Rhodophyceae)、仙菜目(Ceramiales)、松节藻科(Rhodomalaceae)，主要分布于热带、亚热带和温带海域的低潮线附近及深海部分，约135种，中国有20种以上。凹顶藻次级代谢产物的结构类型主要包括倍半萜、二萜、三萜/聚醚和C15-多聚乙酰等，冈村凹顶藻中，倍半萜和C15-多聚乙酰最为常见，且以卤代著称。本文对凹顶藻卤代机制的研究进行了总结，并对最近10年来从凹顶藻中分离到的倍半萜、C15-多聚乙酰类成分及其合成研究进行了综述，同时对采自山东和广东的两种冈村凹顶藻(Laurencia okamurai Yamada)的化学成分进行了比较研究，发现生长在不同地理位置的同种凹顶藻化学成分有很大差异。 干燥并粉碎的冈村凹顶藻(L. okamurai)分别进行有机溶剂提取，粗提物通过硅胶柱层析、凝胶Sephadex LH-20柱层析、反相硅胶柱层析、制备薄层层析等方法分离纯化得单体化合物，利用超导核磁共振、质谱和红外光谱等现代波谱技术鉴定化合物的结构。从上述采自不同地点的冈村凹顶藻中分离鉴定的化合物共计30个，包括新化合物8个，依次是laurenokamurenes A-E (LA1-LA5)，laurenokamurin (LA6)，laurenokaldehyde (LA7)和isochlorolaurenol (LB1)，新天然产物1个 (LA12)和已知化合物21个。其中，采自山东的冈村凹顶藻次级代谢产物结构类型相对复杂多样，从中分离到的化合物包括bisabolane型倍半萜4个，chamigrane型倍半萜5个，laurane型倍半萜6个，C15-多聚乙酰类化合物5个，其他类型化合物1个（见第III页）；从采自广东的冈村凹顶藻中分离鉴定的化合物主要为7个laurane型倍半萜和2个其他类型的化合物（见第IV页）。 对分离鉴定的部分单体化合物进行了抗细菌（金黄色葡萄球菌）活性筛选，结果表明所有的测试样品都不具有抗金黄色葡萄球菌活性。

Chemical Composition and Antimicrobial Activity of the Essential Oil from Rollinia sericea (REFr.) REFr. (Annonaceae) Leaves

The chemical composition of the essential oil of Rollinia sericea (R.E.Fr.) R.E.Fr. leaves was determined by GC and GC/MS analysis. The analysis revealed the presence mainly of sesquiterpenes: beta-elemene (10%), beta-caryophyllene (10.0%), bicyclogermacrene (9.1%), germacrene-D (8.2%), bicycloelemene (6.2%) and (Z)-nerolidol (5.3%). Rollinia sericea oil was able to inhibit the growth of both fungi Aspergillus niger (16404) and Candida albicans (ATCC 10231) as well as the Gram-positive bacterium Staphyloccocus aureus (ATCC 6538) but it was inactive against the Gram-negative bacteria Escherichia coli (ATCC 8739) and Pseudomonas aeruginosa (ATCC 9027).

Annona sp: Plants with multiple applications as alternative medicine - a review

Annona species have been used as a natural remedy for a variety of illnesses with antiparasitic, antispasmodic, antidiarrheal, antiulcer, sedative, analgesic, hypotensive, and vermifugal effects. These properties are due to the presence of a number of bioactive compounds on the leaves, fruit, seeds, and stem. The aim of this review is to show the main species of Annona, their medicinal properties and the chemical constituents that may be related to these effects. In the leaves it is possible to find acetogenins, annopentocins A, B, and C, cis- and trans-annomuricin-D-ones, goniothalamicin, arianacin, and javoricin, related to anticancer properties. Quercetin-3-O-glucoside, also found in the leaves mediates antidiabetic and antioxidative effects. In the fruit are found annonaine, nornuciferine and asimilobine, associated to antidepressive effects. In the seeds are found muricatetrocin A and muricatetrocin B, longifolicin, corossolin, corossolone, uvarigrandin A, bullatacin, squamotatin. These acetogenins are associated with anticancer effects. Cyclosquamosin B, quercetin, and cyclosquamosin from the seeds have respectively vasorelaxant, antithyroidal and, antiinflammatory activity. In the stem parts there are several components as N-trans-feruloyltyramine, N-p-coumaroyltyramine, and N-trans-caffeoyltyramine, lignans, syringaresinol, syringaldehyde, beta-sitosterol and beta-sitosterol-beta-D-glucoside which exhibit antiplatelet aggregation activity. Copaene, patchoulane, 1H-cycloprop (e) azulene and kaur-16-en-19-oic acid found in the barks exhibit significant central as well as peripheral analgesic and antiinflammatory activities. The properties of the biological compounds in Annona species support information that may provide validation for its medicinal uses, but further studies should be performed to establish ideal and safe doses of consumption to ensure the effectiveness of the benefits. © 2012 Bentham Science Publishers.

Genus Xylopia (Annonaceae): Chemical and Biological Aspects

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Insecticidal potential of the annonaceae family plants

The use of plants compounds for the control of insects has increased worldwide. This occurs because the vegetal insecticides contains biodegradable compounds, nontoxic products and potentially suitable for use in pest control. Plants of the family Annonaceae are standing out as biopesticides because they are bioactive naturally in addition to presenting cytotoxic activity, antitumor, vermifuge, antimicrobial, immunosuppressive, anti-emetic, inhibiting appetite, antimalarial and also insecticide. The insecticidal activity of Annonaceae is due to the presence of acetogenins, substances that act on mitochondria inhibiting the NADH -ubiquinone oxidoreductase, causing the death of insects. In this review we report the use of Annonaceae in insect control, showing that so far, only 42 species of Annonaceae have information insecticidal activity against just over 60 species of insect pests. This information shows that much research is still needed, especially to get to know the insecticidal activity of other Annonaceae species, in addition to its effects on insect pests not yet studied. So we will have as an alternative to sustainable development, new vegetal insecticides such as those obtained from different Annonaceae species, which can act as an additional tool to balance the excesses of agriculture chemical or conventional.

Evaluation of the anti-mycobacterium tuberculosis activity and in vivo acute toxicity of annona sylvatic

Background The recent emergence of extensively multidrug-resistant Mycobacterium tuberculosis strains has further complicated the control of tuberculosis. There is an urgent need for the development of new molecular candidates antitubercular drugs. Medicinal plants have been an excellent source of leads for the development of drugs. The aim of this study was to evaluate the in vitro activity of 28 alcoholic extracts and essential oils of native and exotic Brazilian plants against Mycobacterium tuberculosis and to further study these extracts through chemical fractionation, the isolation of their constituents, and an evaluation of the in vivo acute toxicity of the active extracts. To the best of our knowledge this is the first chemical characterization, antituberculosis activity and acute toxicity evaluation of Annona sylvatica. Methods The anti-mycobacterial activity of these extracts and their constituent compounds was evaluated using the resazurin reduction microtiter assay (REMA). To investigate the acute toxicity of these extracts in vivo, female Swiss mice were treated with the extracts at doses of 500, 1000 and 2000 mg · kg-1 of body weight. The extracts were characterized by LC-MS, and the constituents were isolated and identified by chromatographic analysis of spectroscopic data. Results Of the 28 extracts, the methanol extract obtained from the leaves of Annona sylvatica showed anti-mycobacterial activity with an minimal inhibitory concentration (MIC) of 184.33 μg/mL, and the ethyl acetate fraction (EAF) resulting from liquid-liquid partitioning of the A. sylvatica extract showed an MIC of 115.2 μg/mL. The characterization of this extract by LC-MS identified flavonoids and acetogenins as its main constituents. The phytochemical study of the A. sylvatica EAF resulted in the isolation of quercetin, luteolin, and almunequin. Conclusions Among the compounds isolated from the EAF, luteolin and almunequin were the most promising, with MICs of 236.8 μg/mL (827.28 μM) and 209.9 μg/mL (328.48 μM), respectively. The acute administration of the EAF fraction in doses of 500, 1000, and 2000 mg · kg-1 of body weight did not cause signs of toxicity in the treated animals.

Comparative analysis of the corps en cerise in several species of Laurencia (Ceramiales, Rhodophyta) from the Atlantic Ocean

Different species of Laurencia have proven to be a rich source of natural products yielding interesting bioactive halogenated secondary metabolites, such as terpenoids and acetogenins. It is shown that such compounds are accumulated in the spherical, reniform to claviform refractive inclusions called corps en cerise (CC), which are intensively osmiophilic and located mainly in the cortical cells of the thalli and also in trichoblast cells. Up to now, it was believed that CC were present only in these two kinds of cells. Recently, however, a species of Laurencia, L. marilzae, with CC in all cells of the thallus, i.e., cortical, medullary, including the pericentral and axial cells, as well as in the trichoblasts, was described from the Canary Islands, and subsequently also reported to Brazil and Mexico. Within the Laurencia complex, only Laurencia species produce CC. Since the species of Laurencia are targets of interest for the prospection of bioactive substances due to their potential antibacterial, antifungal, anticholinesterasic, antileishmanial, cytotoxic, and antioxidant activities, the present paper carries out a comparative analysis of the corps en cerise in several species of Laurencia from the Atlantic Ocean to obtain basic information that can support natural product bioprospection projects. Our results show that the number and size of the CC are constant within a species, independent of the geographical distribution, corroborating their use for taxonomical purposes to differentiate groups of species that present a lower number from those that have a higher number. In this regard, there was a tendency for the number of CC to be higher in some species of Laurencia from the Canary Islands. The presence of CC can also be used to distinguish species in which these organelles are present in all cells of the thallus from those in which CC are restricted to the cortical cells. Among the species analyzed, L. viridis displayed the most varied secondary metabolites composition, such as sesquiterpenes, diterpenes, triterpenes, all of which showed potent antiviral, cytotoxic, and antitumoral activities, including protein phosphatase type 2A (PP2A) inhibitory effects.