Renata Biegelmeyer

Halisphingosines A and B, Modified Sphingoid Bases from Haliclona tubifera. Assignment of Configuration by Circular Dichroism and van’t Hoff’s Principle of Optical Superposition

Halisphingosines A (1) and B (2), modified long-chain sphingoid bases, from the marine sponge Haliclona tubifera collected in Brazil, were characterized after conversion to their N-Boc derivatives. The 2R,3R,6R configuration of halisphingosine A, a compound first reported from Haliclona sp. from South Korea, was confirmed using a novel CD approach: deconvolution of exciton coupling from mono- and trinaphthoyl derivatives obtained by derivatization of the natural product. The sensitive CD deconvolution method, applicable to submilligram samples, simultaneously predicted the relative and absolute configuration of three stereocenters in halisphingosine A with precision and accuracy. Halisphingosine B was assigned by correlation to halisphingosine A.

In vitro Antioxidant and Enzymatic Approaches to Evaluate Neuroprotector Potential of Blechnum Extracts without Cytotoxicity to Human Stem Cells.

Background: Investigation of selected plant extracts on multi-targets related to neurodegeneration, such as monoamine oxidases (MAO), cholinesterase enzymes, and antioxidant activities (AOA) is a useful tool for identification of new scaffolds. Objective: This work investigated biological effects of three Blechnum methanol extracts from Brazil and chemical profile of the most active sample. Materials and Methods: AOA included scavenging of hydroxyl and nitric oxide radicals, also lipid peroxidation inhibition. Enzymatic modulation of Blechnum binervatum, Blechnum brasiliense, and Blechnum occidentale extracts on MAO and cholinesterases was conducted. Moreover, total phenol content was performed with all samples, and high-performance liquid chromatography-diode array detection mass spectrometry HPLC-DAD-MS analysis was carried out with B. brasiliense. Possible toxic effects were evaluated on Wistar rats polymorphonuclear cells (PMN) and human stem cells. Results: B. brasiliense extract presented the highest phenolic amount (9.25 g gallic acid equivalent/100 g extract) and lowest IC50values (112.3 ± 2.61 and 176.1 ± 1.19 μg/mL) against hydroxyl radicals and on lipid peroxidation, respectively, showing strong AO effects. On nitric oxide assay and cholinesterase inhibition, all extracts were considered inactive. MAO-A selective action was evidenced, being B. brasiliense powerful against this enzyme (IC50: 72.7 μg/mL), followed by B. occidentale and B. binervatum (IC50: 130.85 and 165.2 μg/mL). No cytotoxic effects were observed on PMN and human stem cells treated with Blechnum extracts. HPLC-DAD-MS analysis of B. brasiliense allowed the identification of chlorogenic and rosmarinic acids. Conclusion: Our results especially highlight B. brasiliense, with pronounced phenols content and strong effects on selected targets related to neurodegeneration, being characterized as a natural safe source of bioactive hydroxycinnamic acids. SUMMARY Blechnum crude extracts showed high phenolic amounts and valuable IC50 values on targets related with neurodegenerative disorders Blechnum brasiliense was the most active sample, with strong radical scavenging and lipid peroxidation inhibition, also with monoamine oxidases: A selective modulation No cytotoxic effects were observed on polymorphonuclear cells rat cells and human stem cells treated with Blechnum extracts High-performance liquid chromatography-diode array detection-mass spectrometry analysis of Blechnum brasiliense allowed the identification of hydroxycinnamic derivatives: Chlorogenic and rosmarinic acids. Abbreviations used: IC50: half maximal inhibitory concentration; MAO: monoamine oxidase; MAO-A: monoamine oxidase isoform A; MAO-B: monoamine oxidase isoform B; HO•: hydroxyl radical.

pH-dependent cytotoxic effects of extracts of the marine sponge Polymastia janeirensis on cancer cell lines

Abstract The purpose of this work was to study the cytotoxic effects of marine sponge Polymastia janeirensis, which has been observed in the field to release an orange substance that is toxic to fish. The result showed that aqueous extract (pH 7.0) was highly cytotoxic to glioma (U87) and neuroblastoma (SHSY5Y) cancer cell lines (IC50 < 1.0 μg/mL). In addition, this extract showed potent antioxidant and procoagulant (decreased the clotting time by 1.7-fold) activities. Interestingly, the cytotoxic effects were pH-dependent since the viability of the cancer cells was not affected with the extract (pH 5.5). The close similarity between the aqueous extract (pH 7.0) and the orange liquid that is released by the sponge indicates that this potential chemical defence of P. janeirensis deserves further investigation.

Sphingosines Derived from Marine Sponge as Potential Multi-Target Drug Related to Disorders in Cancer Development.

Haliclona tubifera, marine sponge species abundant in Brazilian coastline, presents only a few papers published in the literature. Recently, we have reported the isolation of two modified C18 sphingoid bases: (2R,3R,6R,7Z)-2-aminooctadec-7-ene-1,3,6-triol and and (2R,3R,6R)-2-aminooctadec-1,3,6-triol. In order to continue our research, in this work aimed at the biological investigation of fractions that led to the isolation of these compounds. We evaluated the cytotoxic effect of marine sponge H. tubifera fractions in glioma (U87) and neuroblastoma (SH-SY5Y) human cell lines. In addition, considering the link between cancer, imbalance of reactive oxygen species and coagulation disorders, we also investigated the in vitro effects on blood coagulation and their redox properties. We showed that the ethyl acetate (EtOAc) fraction, rich in sphingoid bases, had important cytotoxic effects in both cancer cell lines with an IC50 < 15 μg/mL and also can inhibit the production of peroxyl radicals. Interestingly, this fraction increased the recalcification time of human blood, showing anticoagulant properties. The present study indicates the sphingosines fraction as a promising source of chemical prototypes, especially multifunctional drugs in cancer therapy.

Essential oil constituents of Psychotria leiocarpa

The Rubiaceae family is composed mostly of trees, shrubs, or infrequently herbs and comprises about 450 genera and 6.500 species with a complex taxonomy. For Psychotria leiocarpa Cham. & Schltdl., leaves were analyzed for their alkaloid and iridoid content [1–5]. A number of studies have reported different pharmacological effects of Psychotria alkaloids, such as inhibition of the aggregation of human platelets [6], cytotoxicity [7], and analgesic activity [8]. The crude ethanolic extract of P. leiocarpa leaves yielded a nonspecific analgesic activity in the tail flick test [9]. To the best of our knowledge, there are no previous studies dealing with the volatiles of this species. As part of our research on Rubiaceae species [1–5], we now report the chemical composition of the essential oil. Leaves of P. leiocarpa were collected in Osorio, Rio Grande do Sul, South Brazil, in July 2008. A voucher specimen (Carlos 6) was deposited at the herbarium of the Universidade Federal do Rio Grande do Sul (ICN, SOBRAL 7898). The oil was obtained from 100 g of fresh leaves by hydrodistillation using a Clevenger-type apparatus for four hours. The oil obtained had a yield of 0.1%. Analysis of the oil was performed using a Shimadzu GC-17A equipped with Shimadzu GC 10 software, using a DB-5 fused silica capillary column (25 m, 0.25 mm; film thickness 0.25 m). The oven temperature was programmed from 60–300 C at 3 C/min, with helium as carrier gas at an inlet pressure of 80 kPa (1 mL/min). Injector (split mode) and detector temperatures were set at 220 C and 250 C, respectively. The percentage compositions were obtained from electronic integration measurements using flame ionization detection (FID, 250 C). The sample was analyzed by GC/MS in the same chromatographic conditions as described above, using a Shimadzu QP-5000-quadrupole MS system, operating with an ionization energy of 70 eV and an interface temperature of 250 C, with a scan time of 1.25 scans/s and an acquisition mass range of 40.0–650.0 Da. The identification of the oil components was accomplished by comparison of their GC retention indices as well as their mass spectra with corresponding data of authentic compounds or of components of reference oils; some mass spectra were compared with those of the NIST (National Institute of Standards and Technology) computer data library or with spectral data given in the literature [10–13]. Thirty-three compounds were identified, comprising 95.9% of total volatiles for Psychotria leiocarpa leaves (Table 1). The essential oil was characterized exclusively by sesquiterpenes. P. leiocarpa oil consists of a large amount of sesquiterpene hydrocarbons with germacrane and cadinane skeletons, such as bicyclogermacrene (35.6%) and germacrene D (17.6%), respectively.

Potential use of secondary products of the agri-food industry for topical formulations and comparative analysis of antioxidant activity of grape leaf polyphenols

Abstract The aim of the present study was to develop a phytocosmetic using Vitis waste by-products, for use as a topical formulation for skin protection against ultraviolet radiation damage. The study also evaluates the free radical scavenger activity of the crude extracts of dried leaves of Vitis vinifera and Vitis labrusca, as well as the anthocyanins, flavonoid fraction and isolated compounds. Next, release and permeation studies of hydrogels were performed using Franz-type diffusion cells. Flavonoid acted more intensively in TRAP and conjugated dienes antioxidant assays, whereas anthocyanins had higher antioxidant activity in hydroxyl and nitric oxide assay. Only quercetin-3-O-glucuronide (5) was released from hydrogels, and the flavonoid retention in porcine ear skin after eight hours of permeation was below of limit of quantification for this compound. The polyphenols present in Vitis are capable of absorbing UV and visible light, justifying their potential as sunscreens for the development of a phytocosmetic.

Cytotoxic effects on tumour cell lines of fatty acids from the marine sponge Scopalina ruetzleri.

Marine sponges are among the most promising sources of chemically diversified fatty acids (FAs). In addition, several studies have shown the effect of polyunsaturated FAs on cancer therapy. This research carried out a biological and chemical evaluation of the sponge Scopalina ruetzleri collected on the South Brazilian coastline.