Juana Rovirosa

Anti-Proliferative Activity of Meroditerpenoids Isolated from the Brown Alga Stypopodium flabelliforme against Several Cancer Cell Lines

The sea constitutes one of the most promising sources of novel compounds with potential application in human therapeutics. In particular, algae have proved to be an interesting source of new bioactive compounds. In this work, six meroditerpenoids (epitaondiol, epitaondiol diacetate, epitaondiol monoacetate, stypotriol triacetate, 14-ketostypodiol diacetate and stypodiol) isolated from the brown alga Stypopodium flabelliforme were tested for their cell proliferation inhibitory activity in five cell lines. Cell lines tested included human colon adenocarcinoma (Caco-2), human neuroblastoma (SH-SY5Y), rat basophilic leukemia (RBL-2H3), murine macrophages (RAW.267) and Chinese hamster fibroblasts (V79). Antimicrobial activity of the compounds was also evaluated against Staphylococcus aureus, Salmonella typhimurium, Proteus mirabilis, Bacillus cereus, Enterococcus faecalis and Micrococcus luteus. Overall, the compounds showed good activity against all cell lines, with SH-SY5Y and RAW.267 being the most susceptible. Antimicrobial capacity was observed for epitaondiol monoacetate, stypotriol triacetate and stypodiol, with the first being the most active. The results suggest that these molecules deserve further studies in order to evaluate their potential as therapeutic agents.

Isoepitaondiol, a diterpenoid of Stypopodium flabelliforme and the insecticidal activity of stypotriol, epitaondiol and derivatives

Abstract A new diterpenoid of mixed biogenesis; isoepitaondiol, has been isolated together with known diterpenoids and two chromones from the alga Stypopodium flabelliforme collected at Easter Island.

Stereostructure reassignment and absolute configuration of isoepitaondiol, a meroditerpenoid from Stypopodium flabelliforme.

Careful examination of the published NMR data for isoepitaondiol, a meroditerpenoid from Stypopodium flabelliforme, suggests that its published structure 1 must be revised. On the basis of extensive 1D and 2D NMR studies, we now propose that structure 2, with a trans-anti-trans-anti-cis arrangement fits isoepitaondiol diacetate. The relative configuration of 2 was confirmed by single-crystal X-ray diffraction, while the absolute configuration was evidenced by vibrational circular dichroism in combination with DFT B3LYP/DGDZVP calculations.

Tropane alkaloids from Schizanthus hookeri

Abstract Tropine, a pair of diastereoisomeric hygrolines and two new tropane alkaloids; 3α-senecioyloxytropan-6β-ol and 6β-angeloyloxytropan-3α-ol, were isolated from roots of Schizanthus hookeri .

Insecticide and acaricide activities of polyhalogenated monoterpenes from chilean Plocamium cartilagineum

Abstract Four new alicyclic monoterpenes based on the 1-(2-chlorovinyl)-2,4,5-trichloro-1,5-dimethylcyclohexane skeleton were isolated from Plocamium cartilagineum from the Chilean coast, together with four known cyclic monoterpenes. The structure of the new compounds were determined by comparison of the spectral data with those of known compounds. The insecticide/acaricide and fungicide activities of some of the isolated monoterpenes were determined.

The isolation and structure determination of chilenone A, a putative dimer of 2-methyl-3(2H)-furanone from the marine alga

Abstract The isolation of chilenone A from Laurencia chilensis and the determination of its structure by spectral and x-ray crystallographic techniques is described.

The microbiological transformation of some ent-13-epi-manoyl oxide diterpenes by Gibberella fujikuroi

Abstract Incubation of ent -19-hydroxy-13- epi -manoyl oxide with Gibberella fujikuroi afforded ent -12α,19-dihydroxy-13 - epi -manoyl oxide and ent -7β, 12α, 19-trihydroxy-13 - epi -manoyl oxide, the first of which was transformed by chemical methods into varol ( ent -12α-hydroxy-13- epi -manoyl oxide). The incubation of ent -3β-hydroxy-13- epi -manoyl oxide (ribenol) with the same fungus gave the 12β-hydroxy, the 11β-hydroxy and the 11β,12β-dihydroxy derivatives of ribenol, the first of which was identical with varodiol.

Cytotoxic Activity of Halogenated Monoterpenes from Plocamium cartilagineum

Nine halogenated monoterpenes isolated from the red alga Plocamium cartilagineum have been evaluated for their cytotoxic effects on the tumor cell lines CT26 (murine colon adenocarcinoma), SW480 (human colon adenocarcinoma), HeLa (human cervical adenocarcinoma) and SkMel28 (human malignant melanoma) with several multidrug resistance mechanisms and the mammalian non-tumor cell line CHO (Chinese hamster ovary cells). The activities of these compounds were compared with those of the insecticide γ-hexachlorocyclohexane (lindane) due to chemical structure similarities. Compounds 1, 2, 3, and 5 exhibited selective cytotoxicity against colon and cervical adenocarcinoma cells. Interestingly, the effect of compound 3 was specific and irreversible to human colon adenocarcinoma SW480 cells, which overexpress the transmembrane P-glycoprotein often related to chemoresistance. None of the anti-tumor doses of these compounds was cytotoxic against CHO cells. Furthermore, analysis of cellular extracts after incubation with the test compounds and rotenone (positive uptake control) demonstrated the intracellular accumulation of 1, 2, 3, and 5.

The compound 14-keto-stypodiol diacetate from the algae Stypopodium flabelliforme inhibits microtubules and cell proliferation in DU-145 human prostatic cells.

We investigated the effects of the drug 14-keto-stypodiol diacetate (SDA) extracted from the seaweed product Stypopodium flabelliforme, in inhibiting the cell growth and tumor invasive behavior of DU-145 human prostate cells. In addition, the molecular action of the drug on microtubule assembly was analyzed. The effects of this diterpenoid drug in cell proliferation of DU-145 tumor cells in culture revealed that SDA at concentrations of 5 μM decreased cell growth by 14%, while at 45 μM a 61% decrease was found, as compared with control cells incubated with the solvent but in the absence of the drug. To study their effects on the cell cycle, DU-145 cells were incubated with increasing concentrations of SDA and the distribution of cell-cycle stages was analyzed by flow cytometry. Interestingly, the data showed that 14-keto-stypodiol diacetate dramatically increased the proportion of cells in the G2/M phases, and decreased the number of cells at the S phase of mitosis, as compared with appropriate controls. Studies on their action on the in vitro assembly of microtubules using purified brain tubulin, showed that SDA delayed the lag period associated to nucleation events during assembly, and decreased significantly the extent of polymerization. The studies suggest that this novel derivative from a marine natural product induces mitotic arrest of tumor cells, an effect that could be associated to alterations in the normal microtubule assembly process. On the other hand, a salient feature of this compound is that it affected protease secretion and the in vitro invasive capacity, both properties of cells from metastases. The secretion of plasminogen activator (u-PA) and the capacity of DU-145 cells to migrate through a Matrigel-coated membrane were significantly inhibited in the presence of micromolar concentrations of SDA. These results provide new keys to analyze the functional relationships between protease secretion, invasive behavior of tumor cells and the microtubule network.

NEW BUTYROLACTONE FROM A MARINE-DERIVED FUNGUS ASPERGILLUS SP

Four compounds that belong to two structure types, namely dibenzylbutyrolactone and sesterterpenoids, were obtained from the extract of the strain Aspergillus sp. (2P-22), isolated from a marine sponge, Cliona chilensis. Among them, compound 1 was identified as new, namely butylrolactone-VI. The structures of these compounds were characterized on the basis of spectroscopic data. Biological activities of these fungal metabolites, are described.