Brown Alga Stypopodium Zonale Research Articles

Decoding the molecular mechanism of stypoldione against breast cancer through network pharmacology and experimental validation

Breast cancer is the primary factor contributing to female mortality worldwide. The incidence has overtaken lung cancer. It is the most difficult illness due to its heterogeneity and is made up of several subtypes, including Luminal A and B, basal-like, Her-2 overexpressed and TNBC. Amongst different breast carcinoma subtypes, TNBC is the most deadly breast cancer subtype. The hostile nature of TNBC is mainly attributed to its lack of three hormonal receptors and hence lack of targeted therapy. Furthermore, the current diagnostic options like radiotherapy, surgery and chemotherapy render unsuccessful due to recurrence, treatment side effects and drug resistance. The majority of anticancer drugs come from natural sources or is developed from them, making nature a significant source of many medicines. Marine-based constituents such as nucleotides, proteins, peptides, and amides are receiving a lot of interest in the field of cancer treatment due to their bioactive properties. The role of stypoldione in this study as a prospective treatment for breast carcinoma was examined, and we sought to comprehend the molecular means/pathways this chemical employs in breast carcinoma. The most promising possibility for an anti-cancer treatment is stypoldione, a marine chemical produced from the brown alga Stypopodium zonale. We investigated stypoldione's mode of action in breast cancer using the network pharmacology method, and we confirmed our research by using a number of computational tools, including UALCAN, cBioportal, TIMER, docking, and simulation. The findings revealed 92 common targets between the chemical and breast cancer target network. Additionally, we found that stypoldione targets a number of unregulated genes in breast cancer, including: ESR1, HSP90AA1, CXCL8, PTGS2, APP, MDM2, JAK2, KDR, LCK, GRM5, MAPK14, KIT, and several signaling pathways such as FOXO signaling pathway, VEGF pathway, calcium signaling pathway, MAPK/ERK pathway and Neuroactive ligand-receptor interaction. The examined medication demonstrated a strong affinity for the major targets, according to a docking analysis. The best hit compound produced a stable protein–ligand pair, as predicted by molecular dynamics simulations. Our results are supported by the fact that when in-vitro assays were done on melanoma using stypoldione compound it was found that its mechanisms of action involved the PI3K/mTOR/Akt and NF-kB pathways. This study was set out to inspect the possible value of stypoldione as a breast cancer cure and to get a deeper understanding of the molecular mechanisms by which this drug acts on breast cancer.

Natural products from marine red and brown algae against Trypanosoma cruzi

Various extracts obtained from the red alga Plocamium brasiliense (Greville Howe & Taylor), including a fraction containing crude 5-chloro-1-(E)-chlorovinyl-2,4-dibromo-1,5-dimethylcyclohexane (1) and another containing a mixture of halogenated monoterpenes (F), as well as atomaric acid meroditerpene (2) isolated from brown alga Stypopodium zonale (J. V. Lamouroux) Papenfuss, were evaluated for their activity against Trypanosoma cruzi. The cytotoxic and trypanosomicidal effects of these extracts were evaluated in Vero cells and clinically relevant forms of T. cruzi (amastigotes and trypomastigotes). All extracts from P. brasiliense presented low cytotoxicity and moderate trypanosomicidal effects, except for the hydroalcoholic extract. The crude 1 and F fractions had enhanced trypanocidal activity but showed low selectivity. Moreover, atomaric acid (2) was identified as a hit, demonstrating a potent trypanocidal effect reaching an IC50 <10μM against two different DTU (Yand high selectivity index (<10). These results identify marine natural products as promising candidates against Chagas disease.

Inhibitory Effects of the Lipophilic Extracts and An Isolated Meroditerpene of Brown Alga in Pasture Weeds in the Eastern Amazon Region

ABSTRACT: Two lipophilic extracts and atomaric acid (1), an isolated natural product, were obtained from the marine brown alga Stypopodium zonale (Dictyotaceae) to identify and characterize their potential inhibitory effects on the seed germination, radicle elongation, and hypocotyl development of the weeds Mimosa pudica and Senna obtusifolia. The extracts were prepared with hexane and dichloromethane, and atomaric acid (1) was isolated from hexane extract by way of conventional chromatographic methods. During a 15 days period, germination bioassays were performed at 25 oC with a 12 h photoperiod, whereas radicle elongation and hypocotyl development were assayed at 25 oC with a 24 h photoperiod. After, Petri dishes 9.0 cm in diameter were coated with qualitative filter paper, 25 seeds were placed in a germination chamber, while six pregerminated seeds were placed in the Petri dish for 2-3 days. After 10 days, radicle and hypocotyl extension were measured; and the inhibitory potential of the extracts was assessed at 10 ppm and that of the atomaric acid at 5, 10, 15, and 20 ppm. In both M. pudica and S. obtusifolia, dichloromethane extract achieved the greatest rates of inhibition during seed germination (34% and 22%, respectively), radical germination (38% and 30%, respectively), and hypocotyl development (29% and 22%, respectively). At a concentration of 20 ppm, atomaric acid (1) also demonstrated reduced inhibitory potential, with mean values of 58.67% for M. pudica and 48.67% for S. obtusifolia.

Effects of ocean acidification and contact with the brown alga Stypopodium zonale on the settlement and early survival of the coral Porites astreoides

Effects of ocean acidification and contact with the brown alga Stypopodium zonale on the settlement and early survival of the coral Porites astreoides

A non-native macroalga is less attractive for herbivores but more susceptible to light limitation and grazing stress than a comparable native species

It has been suggested that non-native species are more tolerant towards abiotic stress than ecologically comparable native species. Furthermore, non-native marine macroalgae should be under lower grazing pressure than native seaweeds, because they left their co-evolved enemies behind. As a consequence, they generally need to allocate less energy to defences and can invest more into compensating the negative effects of abiotic stress or, assuming that grazing pressure is low but not zero, to defensive reactions following grazer attack. This, in turn, should make them more stress tolerant and less susceptible to herbivory. However, empirical evidence for both concepts is still scarce and very little is known about whether enemy release is commonly associated with an enhanced tolerance towards abiotic or biotic stress. We therefore ran an experimental study that (a) assessed attractiveness for grazers, (b) verified whether short-term low-light stress impairs growth and (c) investigated whether light limitation and previous grazing interactively affect the consumption of two macroalgae from Madeira Island, the native brown alga Stypopodium zonale and the non-native red alga Grateloupia imbricata by the sea urchin Paracentrotus lividus. To come to ecologically meaningful low-light stress levels, pilot studies were performed in order to determine the light compensation point of photosynthesis for each algal species and then we established six light regimes around this point by reducing the amount of incoming light. Simultaneously, we let one sea urchin graze on each algal individual to stimulate a chemical defence in the seaweeds if present. In parallel to this, we kept the same number of algal replicates in the absence of sea urchins. After 21 days, we compared algal growth in the absence of grazers as well as the attractiveness of previously grazed and non-grazed algal material for P. lividus across all light regimes. Algal attractiveness was assessed in no-choice feeding assays. The observation that the non-native alga was less consumed by the grazer than the native species generally confirms the concept of enemy release. However, light limitation reduced growth in the non-native but not in the native seaweed, while previous grazing reduced consumption of the native but enhanced it in case of the non-native alga. These findings do not corroborate the assumption that enemy release can, through the re-allocation of energy, enhance tolerance to abiotic (light limitation) or biotic (grazing) stressors in non-native marine macroalgae.

The Brown Alga Stypopodium zonale (Dictyotaceae): A Potential Source of Anti-Leishmania Drugs.

This study evaluated the anti-Leishmania amazonensis activity of a lipophilic extract from the brown alga Stypopodium zonale and atomaric acid, its major compound. Our initial results revealed high inhibitory activity for intracellular amastigotes in a dose-dependent manner and an IC50 of 0.27 μg/mL. Due to its high anti-Leishmania activity and low toxicity toward host cells, we fractionated the lipophilic extract. A major meroditerpene in this extract, atomaric acid, and its methyl ester derivative, which was obtained by a methylation procedure, were identified by nuclear magnetic resonance (NMR) spectroscopy. Both compounds inhibited intracellular amastigotes, with IC50 values of 20.2 μM (9 μg/mL) and 22.9 μM (10 μg/mL), and selectivity indexes of 8.4 μM and 11.5 μM. The leishmanicidal activity of both meroditerpenes was independent of nitric oxide (NO) production, but the generation of reactive oxygen species (ROS) may be at least partially responsible for the amastigote killing. Our results suggest that the lipophilic extract of S. zonale may represent an important source of compounds for the development of anti-Leishmania drugs.

Intraspecific variation of meroditerpenoids in the brown alga Stypopodium zonale guiding the isolation of new compounds

Intraspecific variation on meroditerpenoids production by the brown marine alga Stypopodium zonale at four different populations along the Brazilian coast was analyzed using Principal Component Analysis over high-performance liquid chromatography profiles from algae extracts. The ordination of the samples by the similarities of their chromatographic traits showed the existence of three chemotypes: (i) the populations Búzios and Abrolhos which were characterized by the presence of atomaric acid (1), (ii) the population Atol das Rocas which contained the compound stypoldione (2), and (iii) the population Marataízes which was characterized by other peaks that guided the isolation of three new meroditerpenoids stypofuranlactone (3), 10,18-dihydroxy-5′a-desmethyl-5′-acetylatomaric acid (4), and the 10-keto-10-deisopropyliden-5′a-desmethyl-5′-acetylatomaric acid (5) together with the known compound the 10-keto-10-deisopropyliden-atomaric acid (6). The structures and relative stereochemistry of 3, 4 and 5 were elucidated by NMR and MS techniques. The observed chemical differences among populations of S. zonale can be related to its geographic distribution and can open an avenue to the discovery of new compounds in algae.

Antiproliferative activity and absolute configuration of zonaquinone acetate from the Jamaican alga Stypopodium zonale.

The chemical investigation of specimens of the Jamaican brown alga Stypopodium zonale led to the isolation of a cytotoxic compound, zonaquinone acetate (1), along with known compounds flabellinone, not previously identified in S. zonale, stypoldione, 5',7'-dihydroxy-2'-pentadecylchromone and sargaol. The structures of the metabolites were established by analysis of the spectral data including 1D and 2D NMR experiments while the stereochemistry of 1 was assessed by VCD measurements. Cytotoxic activity was reported in vitro for 1 against breast cancer and colon cancer cell lines at IC(50) values of 19.22-21.62 μM and 17.11-18.35 μM respectively, comparing favorably with standard treatments tamoxifen (17.22-17.32 μM) and fluorouracil (27.03-31.48 μM). When tested with liver cancer cells (Hep G2), no activity was observed. Weak antioxidant activity was observed with 1 but sargaol exhibited high activity.

Biotransformation of bromosesquiterpenes by marine fungi

Biotransformation of bromosesquiterpenes was investigated with two types of fungi, Rhinocladiella atrovirens NRBC 32362 and also Rhinocladiella sp. K-001, isolated from the Okinawan brown alga Stypopodium zonale. R. atrovirens NRBC 32362 converted aplysistatin 1 into three compounds 5α-hydroxyaplysistatin 4, 5α-hydroxyisoaplysistatin 5 and 9β-hydroxyaplysistatin 6. Transformation of 1, palisadin A 2 and 12-hydroxypalisadin B 3 by Rhinocladiella sp. K-001 gave two compounds, 3,4-dihydroaplysistatin 7 and 9,10-dehydrobromopalisadin A 8.

In vitro Antiviral Effect of Meroditerpenes Isolated from the Brazilian Seaweed Stypopodium zonale (Dictyotales)

The meroditerpenoids atomaric acid (1), epitaondiol (2) and the peroxylactone of 5'a-desmethyl-5'-acetylatomaric acid (3) were isolated from the Brazilian brown alga Stypopodium zonale collected in two localities (Búzios and Marataízes, RJ and ES States). These compounds showed strong anti-HSV-1 activity in vitro but neither of them inhibited the transcriptase reverse enzyme of HIV-1.

Stypolactone, an interesting diterpenoid from the brown alga Stypopodium zonale

A new diterpenoid of mixed biogenesis, stypolactone 8 , containing a tricyclic terpenoid moiety which in combination with its spirolactone ring, leads to a novel carbon skeleton, has been isolated from the brown alga Stypopodium zonale. It's structure and relative stereochemistry were established by spectroscopic evidence and biogenetic considerations.

New terpenoids from the brown alga Stypopodium zonale.

Three new terpenoids, 1a-3a, and the known metabolites atomaric acid, stypoquinonic acid, and 5'a-desmethyl-5'-acetylatomaric acid have been isolated from the tropical brown alga Stypopodium zonale. The structures and relative stereochemistry of the methyl ester of 1a-3a were determined by spectral methods. The methyl ester of 3a exhibits in vitro cytotoxic activity against human lung and colon carcinoma.

Application of Photoinduced Biomimetic Cascade Cyclizations of Terpenoid Polyalkenes for the Synthesis of (±)-Stypoldione

An efficient formal total synthesis of (±)-stypoldione (1) has been accomplished, using photochemically triggered electron transfer to initiate biomimetic-type cascade cyclizations of terpenoid polyalkenes as the key step. (−)-Stypoldione (1) is an antitumoral marine toxin produced by the tropical brown alga Stypopodium zonale.

A new tyrosine kinase inhibitor from the marine brown alga Stypopodium zonale.

From the lipophilic extract of the marine brown alga Stypopodium zonale (Dictyotaceae) the new terpenoid compound stypoquinonic acid (1) together with the known compounds taondiol (2) and atomaric acid (3) were isolated. The structures of all isolates were determined from their spectroscopic data, including 1- and 2-dimensional NMR methods. The new compound, 1, and atomaric acid (3), showed inhibition of tyrosine kinase (p56lck).

Diterpenoid total synthesis, XXXI. Synthesis and absolute configuration of (−)‐stypoldione, a metabolite of Stypopodium zonale

Abstract(S)‐3‐Hydroxy‐2,2‐dimethylcyclohexanone (2) was converted to (−)‐stypoldione (1), the ichthyotoxic and cytotoxic metabolite of the brown alga Stypopodium zonale. The present synthesis established the absolute configuration of (−)‐stypoldione as depicted in 1.

Diterpenoid total synthesis, XXIX. Synthesis of (±)‐14‐deoxystypoldione, an analogue of the marine natural product stypoldione

Abstract(±)‐14‐Deoxystypoldione (2) has been synthesized by starting from geranylacetone. The key step was the construction of the spirobenzofuran moiety by an intramolecular Michael addition (15 → 16). (−)‐Stypoldione is the ichthyotoxic and cytotoxic metabolite of the tropical brown alga Stypopodium zonale (Lamouroux) Papenfuss.

Synthesis of marine toxins. A biomimetic approach to the novel spirobenzoquinonefuran stypoldione

A synthesis of the spirobenzoquinonefuran unit, i.e.(10), present in stypoldione, a novel marine toxin found in the brown alga Stypopodium zonale which shows pronounced narcotic and hyperactive effects upon reef-dwelling fish, is described. The synthesis uses a strategy, viz(17)→(18)→(19)→(11)→(10), which has close similarities to the probable biogenesis of this portion of the natural product (scheme 1). The advanced precursors (30) and (36) for projected syntheses of deoxystypoldione (33) and stypodiol (3) respectively were also prepared, but neither substrate underwent polyene cyclization to the required pentacyclic molecules.

Aplysia sea hare assimilation of secondary metabolites from brown seaweed,Stypopodium zonale

JuvenileAplysia dactylomela were found feeding in abundance on the tropical brown algaStypopodium zonale, a seaweed previously shown to contain numerous unique terpene-quinone natural products. Lipid extracts of these herbivorous mollusks were shown by TLC and HPLC-NMR analyses to contain appreciable quantities of twoS. zonale metabolites as well as one new but closely related compound. Spectroscopic analyses of the new compound in concert with functional group modifications identified this new compound as 3-keto epitaondiol. A careful analysis of the seaweed extract failed to locate this ketone, and thus, it most likely represents anAplysia-biotransformed compound. This is the first clear reported observation of metabolite transfer between an alga of the phylum Phaeophyta and a sea hare.

Plant defense associations in the marine environment

In contrast to terrestrial systems, few positive plant-plant associations have been recorded in tropical reef environments. This study, conducted at Carrie Bow Cay, Belize during 28 March–10 April 1984, provides the first documentation of herbivore escapes for natural combinations of palatable and unpalatable marine plants. For example, there was a highly significant association of several macrophyte taxa (Laurencia poitei, Dictyota spp., Amphiroa fragilissima, Cladophoropsis macromeres, Galaxaura cylindrica, rhodophycean turf) within a 2.0-cm radius of the herbivore-resistant brown alga Stypopodium zonale. Almost twice as many taxa occurred within 10 cm of S. zonale as within 10 cm of an equal number of random Stypopodium-free points, and there were no algal species negatively associated with S. zonale. The association of A. tribulus, L. poitei, Digenia simplex, rhodophycean turf, and Jania adherens with S. zonale provided them a fourfold greater survivorship per 48 h in the presence of grazing activity by fishes (mainly Acanthuridae and Scaridae). Reduced herbivory by fishes on macroalgae associated with S. zonale was not solely a consequence of its structural aspect. Losses of the palatable alga Acanthophora spicifera were significantly greater for thalli spatially remote (30 and 60 cm) from either a real or simulated Stypopodium; however, losses of A. spicifera adjacent to actual Stypopodium plants were significantly less than the losses next to models. The inter-relationships studied here, where an abundant and well-defended plant provides a significant refuge habitat for at least five relatively edible macroalgae, clearly facilitates the survival of certain taxa in the reef system and concomitantly enhances the within habitat diversity. Our findings also suggest an interaction counter to the process of competitive exclusion, since the single predominant plant has a positive rather than negative net effect on the abundances of other species that utilize the same general resources (e.g., light, space, nutrients).

Pharmacological properties of a marine natural product, stypoldione, obtained from the brown alga Stypopodium zonale

Pharmacological properties of a marine natural product, stypoldione, obtained from the brown alga Stypopodium zonale