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1.
J Chem Ecol ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38958678

ABSTRACT

Characteristics such as calcareous morphology and life cycle are used to understand the ecology of calcified rhodophytes. However, there is limited information regarding their chemical profiles and biological activities. Therefore, a systematic review (PRISMA) was conducted to assess the influence of the chemistry of calcareous rhodophytes on ecological interactions in the marine environment. The keywords used were: ["Chemical AND [Ecology OR Interaction OR Response OR Defense OR Effect OR Cue OR Mediated OR Induce]"] AND ["Red Seaweed" OR "Red Macroalgae" OR Rhodophy?] AND [Calcified OR Calcareous] in Science Direct, Scielo, PUBMED, Springer, Web of Science, and Scopus. Only English articles within the proposed theme were considered. Due to the low number of articles, another search was conducted with three classes and 16 genera. Finally, 67 articles were considered valid. Their titles, abstracts, and keywords were analyzed using IRaMuTeQ through factorial, hierarchical and similarity classification. Most of the studies used macroalgae thallus to evaluate chemical mediation while few tested crude extracts. Some substances were noted as sesquiterpene (6-hydroxy-isololiolide), fatty acid (heptadeca5,8,11-triene) and dibromomethane. The articles were divided into four classes: Herbivory, Competition, Settlement/Metamorphosis, and Epiphytism. Crustose calcareous algae were associated with studies of Settlement/Metamorphosis, while calcified algae were linked to herbivory. Thus, the importance of chemistry in the ecology of these algae is evident,and additional studies are needed to identify the substances responsible for ecological interactions. This study collected essential information on calcified red algae, whose diversity appears to be highly vulnerable to the harmful impacts of ongoing climate change.

2.
Fish Shellfish Immunol ; 134: 108622, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36803779

ABSTRACT

The brown mussel Perna perna is a valuable fishing resource, primarily in tropical and subtropical coastal regions. Because of their filter-feeding habits, mussels are directly exposed to bacteria in the water column. Escherichia coli (EC) and Salmonella enterica (SE) inhabit human guts and reach the marine environment through anthropogenic sources, such as sewage. Vibrio parahaemolyticus (VP) is indigenous to coastal ecosystems but can be harmful to shellfish. In this study, we aimed to assess the protein profile of the hepatopancreas of P. perna mussel challenged by introduced - E. coli and S. enterica - and indigenous marine bacteria - V. parahaemolyticus. Bacterial-challenge groups were compared with non-injected (NC) and injected control (IC) - that consisted in mussels not challenged and mussels injected with sterile PBS-NaCl, respectively. Through LC-MS/MS proteomic analysis, 3805 proteins were found in the hepatopancreas of P. perna. From the total, 597 were significantly different among conditions. Mussels injected with VP presented 343 proteins downregulated compared with all the other conditions, suggesting that VP suppresses their immune response. Particularly, 31 altered proteins - upregulated or downregulated - for one or more challenge groups (EC, SE, and VP) compared with controls (NC and IC) are discussed in detail in the paper. For the three tested bacteria, significantly different proteins were found to perform critical roles in immune response at all levels, namely: recognition and signal transduction; transcription; RNA processing; translation and protein processing; secretion; and humoral effectors. This is the first shotgun proteomic study in P. perna mussel, therefore providing an overview of the protein profile of the mussel hepatopancreas, focused on the immune response against bacteria. Hence, it is possible to understand the immune-bacteria relationship at molecular levels better. This knowledge can support the development of strategies and tools to be applied to coastal marine resource management and contribute to the sustainability of coastal systems.


Subject(s)
Perna , Vibrio parahaemolyticus , Humans , Animals , Escherichia coli , Proteomics , Ecosystem , Chromatography, Liquid , Tandem Mass Spectrometry , Bacteria , Immunity
3.
Mar Drugs ; 21(9)2023 Sep 04.
Article in English | MEDLINE | ID: mdl-37755097

ABSTRACT

Dictyotaceae algae have gained recognition as prolific producers of diterpenes, which are molecules with significant biotechnological potential. These diterpenes hold immense promise as potential active drug components, making the algae a compelling area of study. The present review aims to present the latest advancements in understanding the biopotential of Brazilian Dictyota and Canistrocarpus brown algae, shedding light on the remarkable diversity and the biological and pharmacological potential of the secondary metabolites they produce. A total of 78 articles featuring 26 distinct diterpenes are reported in this review, with their antiviral potential being the mosthighlighted biological activity. Despite considerable research on these algae and their diterpenes, significant knowledge gaps persist. Consequently, the present review is poised to serve as a pivotal resource for researchers who are actively engaged in the pursuit of active diterpenes beyond the immediate purview. Furthermore, it holds the potential to catalyze an increase in research endeavors centered around these algal species within the geographical confines of the Brazilian coastline. Also, it assumes a critical role in directing future scientific explorations toward a better comprehension of these compounds and their ecological implications.


Subject(s)
Diterpenes , Phaeophyceae , Brazil , Antiviral Agents , Biotechnology , Diterpenes/pharmacology
4.
J Environ Sci (China) ; 111: 412-428, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34949370

ABSTRACT

The brown mussel Perna perna (Linnaeus, 1758) is a valuable resource for aquaculture in tropical and subtropical coastal regions. It presents desirable characteristics for biomonitoring, including being sessile, widely distributed and abundant, and is a filter-feeder able to accumulate several classes of pollutants (e.g., metals, hydrocarbons, among others). Mussels' biological responses to pollution exposure can be measured as biomarkers, which include alterations ranging from molecular to physiological levels, to estimate the degree of environmental contamination and its effects on biota. This full review compiles two decades (2000-2020) of literature concerning biological effects on P. perna mussel caused by environmental pollutants (i.e., metals, hydrocarbons, and emerging pollutants), considering environmental and farm-based biomonitoring. Biochemical markers related to mussels' oxidative status were efficient for the biomonitoring of metals (i.e., antioxidant enzymes associated with oxidative damage in biomolecules). Genotoxicity and cytotoxicity indicators (i.e., comet, micronucleus, and neutral red assays) provided a depiction of hydrocarbon contamination. The neutral red assay gave a time-concentration cytotoxic response to a wide range of pollutants, including emerging pollutants (e.g., pharmaceuticals and biocides) and hydrocarbons. Perna perna hemocyte parameters provided a useful approach for biocide biomonitoring. This paper summarizes useful biomarkers from molecular to physiological levels in this mussel species used to identify and quantify the degree of coastal pollution. An integrated biomarker analysis may provide a way to overcome possible biomarker variations and assess multi-polluted sites. Nevertheless, it is necessary to investigate biomarker variations according to natural factors (e.g., season and gonad maturation stage) to standardize them for trustworthy biomonitoring.


Subject(s)
Perna , Water Pollutants, Chemical , Animals , Biomarkers , Environmental Monitoring , Environmental Pollution , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/toxicity
5.
J Chem Ecol ; 44(1): 72-94, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29273953

ABSTRACT

Despite the many publications concerning the isolation of substances and the many reviews of marine natural products, some groups of organisms remain poorly studied, including "Polychaeta". In response, this review covers articles published through December 2016 that address marine natural products produced from polychaetes, with a focus on antipredatory strategies, competitors, fouling, and pathogens. A total of 121 compounds were isolated from 1934 to 2016, which includes halogenated aromatics, proteins, amino acids and Lumazine derivatives most notably-with a defensive function were found in the literature, most frequently in the families Sabellidae, Terebellidae, Glyceridae, and Nereididae. The period of highest discovery of natural products in defensive actions for the group was the 2000s. Polychaetes were addressed in 26 revisions of the total 51 articles analyzed and are less reported than other marine invertebrates such as sponges, cnidarians, mollusks, and tunicates. In sum, the present review provides a basis for future research on the marine chemical ecology of polychaetes.


Subject(s)
Aquatic Organisms/chemistry , Biological Products/chemistry , Animals , Aquatic Organisms/metabolism , Biological Products/isolation & purification , Cnidaria/chemistry , Cnidaria/metabolism , Consummatory Behavior/physiology , Echinodermata/chemistry , Echinodermata/metabolism , Ecological and Environmental Phenomena , Mollusca/chemistry , Mollusca/metabolism , Urochordata/chemistry , Urochordata/metabolism
6.
Mar Drugs ; 14(9)2016 Sep 08.
Article in English | MEDLINE | ID: mdl-27618071

ABSTRACT

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.


Subject(s)
Antiprotozoal Agents/chemistry , Antiprotozoal Agents/pharmacology , Leishmania/drug effects , Leishmaniasis/drug therapy , Phaeophyceae/chemistry , Animals , Diterpenes/pharmacology , Leishmaniasis/parasitology , Macrophages/drug effects , Macrophages/parasitology , Magnetic Resonance Spectroscopy , Mice , Nitric Oxide/biosynthesis , Reactive Oxygen Species/metabolism
7.
Molecules ; 20(3): 3515-26, 2015 Feb 18.
Article in English | MEDLINE | ID: mdl-25699595

ABSTRACT

Snake venoms are composed of a complex mixture of active proteins and peptides which induce a wide range of toxic effects. Envenomation by Bothrops jararaca venom results in hemorrhage, edema, pain, tissue necrosis and hemolysis. In this work, the effect of a mixture of two secodolastane diterpenes (linearol/isolinearol), previously isolated from the Brazilian marine brown alga, Canistrocarpus cervicornis, was evaluated against some of the toxic effects induced by B. jararaca venom. The mixture of diterpenes was dissolved in dimethylsulfoxide and incubated with venom for 30 min at room temperature, and then several in vivo (hemorrhage, edema and lethality) and in vitro (hemolysis, plasma clotting and proteolysis) assays were performed. The diterpenes inhibited hemolysis, proteolysis and hemorrhage, but failed to inhibit clotting and edema induced by B. jararaca venom. Moreover, diterpenes partially protected mice from lethality caused by B. jararaca venom. The search for natural inhibitors of B. jararaca venom in C. cervicornis algae is a relevant subject, since seaweeds are a rich and powerful source of active molecules which are as yet but poorly explored. Our results suggest that these diterpenes have the potential to be used against Bothropic envenomation accidents or to improve traditional treatments for snake bites.


Subject(s)
Blood Coagulation/drug effects , Diterpenes/pharmacology , Edema/drug therapy , Hemolysis/drug effects , Hemorrhage/drug therapy , Proteolysis/drug effects , Snake Venoms/toxicity , Animals , Antivenins/pharmacology , Bothrops/physiology , Diterpenes/isolation & purification , Mice , Mice, Inbred BALB C , Phaeophyceae/growth & development , Phaeophyceae/metabolism
8.
Bioorg Med Chem Lett ; 24(18): 4381-4383, 2014 Sep 15.
Article in English | MEDLINE | ID: mdl-25176328

ABSTRACT

Research on dolabellane diterpenes of brown algae Dictyota spp. has shown that these diterpenoids have strong anti-HIV-1 activity, but there are not data about antiviral activity of dolabellane diterpenes isolated from octocorals, which are antipodes of those isolated from the brown algae. Dolabellanes 13-keto-1(R),11(S)-dolabella-3(E),7(E),12(18)-triene (1) and ß-Araneosene (2) were isolated from the Caribbean octocoral Eunicea laciniata, and both showed low anti-HIV-1 activity and low toxicity. Since it was shown that oxygenated dolabellanes from algae have better anti-HIV-1 activity, in this work some derivatives of the main dolabellane of E. laciniata1 were obtained by epoxidation (3), epoxide opening (4), and allylic oxidation (5). The derivatives showed significant improvement in the anti-HIV-1potency (100-fold), being compounds 3 and 5 the most active ones. Their high antiviral activities, along with their low cytotoxicity, make them promissory antiviral compounds; and it is worth noting that the absolute configuration at the ring junction in the dolabellane skeleton does not seem to be determinant in the antiviral potency of these diterpeneoids.


Subject(s)
Anti-HIV Agents/pharmacology , Diterpenes/chemistry , HIV/drug effects , Oxygen/chemistry , Anti-HIV Agents/chemical synthesis , Anti-HIV Agents/chemistry , Cell Line, Transformed , Dose-Response Relationship, Drug , Humans , Microbial Sensitivity Tests , Molecular Conformation , Structure-Activity Relationship
9.
Mar Drugs ; 12(5): 2471-84, 2014 Apr 30.
Article in English | MEDLINE | ID: mdl-24796305

ABSTRACT

Cardiovascular diseases represent a major cause of disability and death worldwide. Therapeutics are available, but they often have unsatisfactory results and may produce side effects. Alternative treatments based on the use of natural products have been extensively investigated, because of their low toxicity and side effects. Marine organisms are prime candidates for such products, as they are sources of numerous and complex substances with ecological and pharmacological effects. In this work, we investigated, through in vitro experiments, the effects of three diterpenes (pachydictyol A, isopachydictyol A and dichotomanol) from the Brazilian marine alga, Dictyota menstrualis, on platelet aggregation and plasma coagulation. Results showed that dichotomanol inhibited ADP- or collagen-induced aggregation of platelet-rich plasma (PRP), but failed to inhibit washed platelets (WP). In contrast, pachydictyol A and isopachydictyol A failed to inhibit the aggregation of PRP, but inhibited WP aggregation induced by collagen or thrombin. These diterpenes also inhibited coagulation analyzed by the prothrombin time and activated partial thromboplastin time and on commercial fibrinogen. Moreover, diterpenes inhibited the catalytic activity of thrombin. Theoretical studies using the Osiris Property Explorer software showed that diterpenes have low theoretical toxicity profiles and a drug-score similar to commercial anticoagulant drugs. In conclusion, these diterpenes are promising candidates for use in anticoagulant therapy, and this study also highlights the biotechnological potential of oceans and the importance of bioprospecting to develop medicines.


Subject(s)
Anticoagulants/pharmacology , Diterpenes/pharmacology , Phaeophyceae/chemistry , Platelet Aggregation Inhibitors/pharmacology , Anticoagulants/isolation & purification , Blood Coagulation/drug effects , Collagen/pharmacology , Diterpenes/chemistry , Diterpenes/isolation & purification , Humans , Hydrolysis , In Vitro Techniques , Platelet Aggregation/drug effects , Platelet Aggregation Inhibitors/isolation & purification , Thrombin/pharmacology
10.
Mar Drugs ; 12(7): 4247-59, 2014 Jul 23.
Article in English | MEDLINE | ID: mdl-25056631

ABSTRACT

The marine brown alga Dictyota pfaffii from Atol das Rocas, in Northeast Brazil is a rich source of dolabellane diterpene, which has the potential to be used in future antiviral drugs by inhibiting reverse transcriptase (RT) of HIV-1. Reexamination of the minor diterpene constituents yielded three new dolabellane diterpenes, (1R*,2E,4R*,7S,10S*,11S*,12R*)10,18-diacetoxy-7-hydroxy-2,8(17)-dolabelladiene (1), (1R*,2E,4R*,7R*,10S*,11S*,12R*)10,18-diacetoxy-7-hydroxy-2,8(17)-dolabelladiene (2), (1R*,2E,4R*,8E,10S*,11S,12R*)10,18-diacetoxy-7-hydroxy-2,8-dolabelladiene (3), termed dolabelladienols A-C (1-3) respectively, in addition to the known dolabellane diterpenes (4-6). The elucidation of the compounds 1-3 was assigned by 1D and 2D NMR, MS, optical rotation and molecular modeling, along with the relative configuration of compound 4 and the absolute configuration of 5 by X-ray diffraction. The potent anti-HIV-1 activities displayed by compounds 1 and 2 (IC50 = 2.9 and 4.1 µM), which were more active than even the known dolabelladienetriol 4, and the low cytotoxic activity against MT-2 lymphocyte tumor cells indicated that these compounds are promising anti-HIV-1 agents.


Subject(s)
Anti-HIV Agents/isolation & purification , Diterpenes/isolation & purification , Phaeophyceae/metabolism , Anti-HIV Agents/chemistry , Anti-HIV Agents/pharmacology , Diterpenes/chemistry , Diterpenes/pharmacology , HIV-1/drug effects , Magnetic Resonance Spectroscopy
11.
Nat Prod Res ; : 1-6, 2023 Dec 06.
Article in English | MEDLINE | ID: mdl-38054811

ABSTRACT

Herpes simplex virus type 2 (HSV-2) is the most common agent of sexually transmitted infections around the world. Currently, no vaccine is available, and acyclovir is the reference compound in treatment HSV-2 infections. However, the emergence of resistant strains has reduced the efficacy in treatment. Several studies have shown marine seaweed biological activities, but there are no studies yet about the activity anti-HSV-2 of two its secundary metabolites, atomaric acid (1) and marine dolastane (2), isolated from Stypopodium zonale and Canistrocarpus cervicornis respectively. Therefore, we evaluated the anti-HSV-2 activity of compounds 1 and 2. Both compounds showed anti-HSV-2 activity with low cytotoxicity and compound 1 inactivated 90% of the viral particles at 50 µM. Both compounds inhibited the penetration and results in silico indicated the compound 1 as possible therapy alternative anti -HSV-2.

12.
Nat Prod Res ; 36(22): 5783-5787, 2022 Nov.
Article in English | MEDLINE | ID: mdl-34930073

ABSTRACT

HIV is a public health problem, which makes necessary the development of new drugs. Natural products are known for their anti-HIV potential and a good strategy to suggest its mechanism of action is using in silico tools. Herein, diterpenes 1-3 had the binding mode evaluated in the HIV-1 glycoprotein; and properties ADMET in silico performed. In molecular docking important interactions between the hydrophobic cavity, and 1 and 2 were observed. In the molecular dynamics, 1 remained stable covering the entire hydrophobic cavity and performed hydrogen bond during all simulation. ADMET evaluation showed good properties for the diterpenes. Based on these findings, it was possible to suggest the potential from natural products as entry inhibitor and HIV-1 treatment.


Subject(s)
Biological Products , Diterpenes , HIV-1 , Phaeophyceae , Molecular Docking Simulation , Phaeophyceae/chemistry , Diterpenes/chemistry
13.
J Thromb Thrombolysis ; 31(2): 235-40, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21210185

ABSTRACT

Marine brown algae of the family Dictyotaceae are rich sources of monocyclic, bicyclic, and tricyclic diterpenes. These molecules are responsible for a wide range of pharmacological and ecological functions, as antitumor and antiviral. Here, we analyzed the effect of the dolastane diterpene (4R, 9S, 14S)-4α-Acetoxy-9ß,14α-dihydroxydolast-1(15),7-diene, isolated from the marine brown alga, Canistrocarpus cervicornis on blood clotting and platelet aggregation. The dolastane diterpene was able to inhibit either plasma or fibrinogen coagulation induced by thrombin as well as delayed coagulation in the recalcification test. The dolastane diterpene impaired, in a concentration-dependent manner platelet aggregation induced by collagen or adenosine diphosphate with no lysis on such cells. Thus, the dolastane diterpene maybe a promising source of natural inhibitors for hemostatic disturbs (clotting and platelet aggregation) leading to the discovery of drugs of potential use as antithrombotic and antiplatelet. In addition, the dolastane diterpene may be used as a molecular model for development of new antithrombotic agents giving new approaches to the management to the treatment of thrombotic disturbs.


Subject(s)
Anticoagulants , Blood Coagulation/drug effects , Diterpenes , Phaeophyceae/chemistry , Platelet Aggregation Inhibitors , Platelet Aggregation/drug effects , Anticoagulants/chemistry , Anticoagulants/pharmacology , Diterpenes/chemistry , Diterpenes/pharmacology , Humans , Platelet Aggregation Inhibitors/chemistry , Platelet Aggregation Inhibitors/pharmacology
14.
Mar Drugs ; 9(8): 1346-1358, 2011.
Article in English | MEDLINE | ID: mdl-21892349

ABSTRACT

The ischemic disorders, in which platelet aggregation and blood coagulation are involved, represent a major cause of disability and death worldwide. The antithrombotic therapy has unsatisfactory performance and may produce side effects. So, there is a need to seek molecules with antithrombotic properties. Marine organisms produce substances with different well defined ecological functions. Moreover, some of these molecules also exhibit pharmacological properties such as antiviral, anticancer, antiophidic and anticoagulant properties. The aim of this study was to evaluate, through in vitro tests, the effect of two extracts of brown algae and ten marine sponges from Brazil on platelet aggregation and blood coagulation. Our results revealed that most of the extracts were capable of inhibiting platelet aggregation and clotting measured by plasma recalcification tests, prothrombin time, activated partial thromboplastin time, and fibrinogenolytic activity. On the other hand, five of ten species of sponges induced platelet aggregation. Thus, the marine organisms studied here may have molecules with antithrombotic properties, presenting biotechnological potential to antithrombotic therapy. Further chemical investigation should be conducted on the active species to discover useful molecules for the development of new drugs to treat clotting disorders.


Subject(s)
Anticoagulants/chemistry , Anticoagulants/pharmacology , Phaeophyceae/chemistry , Platelet Aggregation Inhibitors/chemistry , Platelet Aggregation Inhibitors/pharmacology , Porifera/chemistry , Animals , Blood Coagulation/drug effects , Brazil , Fibrinolytic Agents/chemistry , Fibrinolytic Agents/pharmacology , Humans , Platelet Aggregation/drug effects , Prothrombin Time
15.
Biol Bull ; 240(3): 157-168, 2021 06.
Article in English | MEDLINE | ID: mdl-34129443

ABSTRACT

AbstractAlthough researchers have examined numerous marine organisms' compensatory characteristics to minimize predation pressure, few have investigated the defensive mechanisms of polychaetes, despite their diversity. Thus, our study's aim was to evaluate the palatability and defensive strategies, both chemical and structural, in the polychaetes Branchiomma luctuosum, Perinereis anderssoni, Phragmatopoma caudata, Eurythoe complanata, and Timarete sp. Another twofold aim was to determine, by comparing our results with the literature, any latitudinal difference in the defensive strategies of E. complanata and to assess defensive mechanisms and palatability in relation to individuals' mobility, overtness, body regionalization, and color. Specimens were collected at Boa Viagem and Itaipu Beaches in Niterói, Rio de Janeiro, Brazil. In assays, a generalist consumer, the hermit crab Calcinus tibicen, was used to evaluate palatability and defenses. In palatability assays of live tissue of the polychaetes, consumers were offered a fresh piece of each polychaete to gauge their acceptance or rejection; in artificial food assays to test extracts of the polychaetes, artificial bait containing extracts of the polychaetes was offered to crabs to identify any chemical defense. Although the extracts of B. luctuosum, E. complanata, P. caudata (i.e., opercular crown), and Timarete sp. were not palatable to the consumers, extracts of P. anderssoni and P. caudata (i.e., body) were. Moreover, the opercular crown of P. caudata and the branchial crown of B. luctuosum showed evidence of structural and chemical defenses. The results corroborate past findings, suggesting no latitudinal variation in the defensive strategies of E. complanata. In general, less motile and more exposed species, aposematic or dark in color, exhibited greater investment in defensive strategies and unpalatability.


Subject(s)
Polychaeta , Animals , Aquatic Organisms , Brazil , Humans , Predatory Behavior
16.
Sci Rep ; 10(1): 8263, 2020 05 19.
Article in English | MEDLINE | ID: mdl-32427940

ABSTRACT

The lack of vaccines and antiviral treatment, along with the increasing number of cases of Zika virus (ZIKV) and Chikungunya virus (CHIKV) infections, emphasize the need for searching for new therapeutic strategies. In this context, the marine brown seaweed Canistrocarpus cervicornis has been proved to hold great antiviral potential. Hence, the aim of this work was to evaluate the anti-ZIKV and anti-CHIKV activity of a marine dolastane isolated from brown seaweed C. cervicornis and its crude extract. Vero cells were used in antiviral assays, submitted to ZIKV and CHIKV, and treated with different concentrations of C. cervicornis extract or dolastane. The crude extract of C. cervicornis showed inhibitory activities for both ZIKV and CHIKV, with EC50 values of 3.3 µg/mL and 3.1 µg/mL, respectively. However, the isolated dolastane showed a more significant and promising inhibitory effect (EC50 = 0.95 µM for ZIKV and 1.3 µM for CHIKV) when compared to both the crude extract and ribavirin, which was used as control. Also, the dolastane showed a very potent virucidal activity against CHIKV and was able to inhibit around 90% of the virus infectivity at 10 µM. For the ZIKV, the effects were somewhat lower, although interesting, at approximately 64% in this same concentration. Further, we observed that both the extract and the dolastane were able to inhibit the replication of ZIKV and CHIKV at different times of addition post-infection, remaining efficient even if added after 8 hours post-infection, but declining soon after. A synergistic effect using sub-doses of the extract and isolates was associated with ribavirin, inhibiting above 80% replication even at the lowest concentrations. Therefore, this work has unveiled the anti-ZIKV and CHIKV potential of C. cervicornis crude extract and an isolated dolastane, which, in turn, can be used as a preventive or therapeutic strategy in the future.


Subject(s)
Antiviral Agents/pharmacology , Chikungunya virus/drug effects , Phaeophyceae/chemistry , Plant Extracts/pharmacology , Seaweed/chemistry , Virus Replication/drug effects , Zika Virus/drug effects , Animals , Antiviral Agents/chemistry , Chikungunya Fever/virology , Chikungunya virus/physiology , Chlorocebus aethiops , Humans , Plant Extracts/chemistry , Vero Cells , Zika Virus/physiology , Zika Virus Infection/virology
17.
Phytother Res ; 23(7): 943-7, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19142983

ABSTRACT

The dolastane diterpenes 4-acetoxy-9,14-dihydroxydolast-1(15),7-diene (1) and 4,7-diacetoxy-14-hydroxydolast-1(15),8-diene (2) were isolated from specimens of the alga Dictyota cervicornis collected from the Rio de Janeiro coast, Brazil. Chemical structures of the diterpenes were assigned by 1D and 2D NMR spectral data for the first time. Both substances inhibited Na(+)K(+)-ATPase preparations from guinea-pig brain or kidney, with the same inhibitory potency towards enzyme isoforms. The maximal inhibition obtained for 1 was 40% at a concentration of 0.5 mm in the incubation mixture, while it reached 80% for compound 2 at this concentration. Ouabain insensitive ATPases were inhibited by 1, but not by 2. Data comparing the inhibitory potency of these compounds with that of ouabain and oleic acid suggest a higher degree of selectivity of 2 towards the Na(+)K(+)-pump. Cardiac glycosides such as ouabain are used classically in the treatment of heart failure, but alterations of Na(+)K(+)-pump activity are also involved in several other diseases. Therefore, the study of compounds interfering with this pump activity is gaining further importance.


Subject(s)
Diterpenes/pharmacology , Enzyme Inhibitors/pharmacology , Phaeophyceae/chemistry , Sodium-Potassium-Exchanging ATPase/antagonists & inhibitors , Animals , Diterpenes/isolation & purification , Enzyme Inhibitors/isolation & purification , Guinea Pigs , Molecular Structure , Sodium-Potassium-Exchanging ATPase/metabolism
18.
Front Microbiol ; 10: 2426, 2019.
Article in English | MEDLINE | ID: mdl-31708898

ABSTRACT

Chikungunya virus (CHIKV) infection is one of the most challenging re-emergent diseases caused by a virus, and with no specific antiviral treatment it has now become a major public health concern. In this investigation, 25 blood samples were collected from patients with characteristic CHIKV symptoms and submitted to a virus isolation protocol, which detected 3 CHIKV isolates. These samples were evaluated by sequencing for the characterization of the strains and any homology to viruses circulating in Brazil during a recent outbreak. These viruses were used for the development of antiviral assays. Subsequently, the inhibitory effects of seaweed extracts on CHIKV replication were studied. The marine species of algae tested were Bryothamnion triquetrum, Caulerpa racemosa, Laurencia dendroidea, Osmundaria obtusiloba, Ulva fasciata, and Kappaphycus alvarezii, all of which are found in different countries including Brazil. The results revealed high levels of CHIKV inhibition, including extracts of O. obtusiloba with inhibition values of 1.25 µg/mL and a selectivity index of 420. Viral inhibition was dependent on the time of addition of extract of O. obtusiloba to the infected cells, with the optimal inhibition occurring up to 16 h after infection. Neuron evaluations with O. obtusiloba were performed and demonstrated low toxicity, and in infected neurons we observed high inhibitory activity in a dose-dependent manner. These results indicate that the algal extracts may be promising novel candidates for the development of therapeutic agents against CHIKV infections.

19.
Molecules ; 13(6): 1253-62, 2008 Jun 04.
Article in English | MEDLINE | ID: mdl-18596652

ABSTRACT

The crude extract of the Brazilian brown alga Dictyota crenulata was analyzed by NMR spectroscopy and HRGC-MS techniques. Seven diterpenes were identified: pachydictyol A, dictyodial, 4beta-hydroxydictyodial A, 4beta-acetoxydictyodial A, isopachydictyol A, dictyol C and dictyotadiol. Xeniane diterpenes have previously been found in D. crenulata from the Pacific Ocean. The results characterize D. crenulata as a species that provides prenylated guaiane (group I) and xeniane diterpenes (group III), thus making it a new source of potential antiviral products.


Subject(s)
Diterpenes/isolation & purification , Phaeophyceae/chemistry , Antiviral Agents/isolation & purification , Diterpenes/analysis , Gas Chromatography-Mass Spectrometry , Magnetic Resonance Spectroscopy , Sesquiterpenes, Guaiane
20.
Article in English | MEDLINE | ID: mdl-25699078

ABSTRACT

BACKGROUND: Snakebite is considered a neglected tropical disease by the World Health Organization. In Brazil, about 70% of the envenomation cases are caused by Bothrops snakes. Its venom may provoke hemorrhage, pain, necrosis, hemolysis, renal or cardiac failure and even death in victims. Since commercial antivenom does not efficiently neutralize the local toxic effects of venoms, natural products have been tested in order to provide alternative or complementary treatment to serum therapy. Therefore, the present study aimed to evaluate the ability of the seaweed Plocamium brasiliense and its active derivatives to neutralize hemorrhagic, edematogenic, hemolytic, coagulant and proteolytic activities of B. jararaca venom. METHODS: Specimens of P. brasiliense were collected in Rio de Janeiro state, Brazil, dried and submitted to oil extraction using four solvents of increasing polarities, n-hexane (HEX), dichloromethane (DCM), ethyl acetate (ETA) and hydroalcoholic solution (HYD). The solvents were evaporated, yielding HEX, DCM, ETA and HYD extracts. Further, all extracts were dissolved in dimethylsulfoxide. In addition, two monoterpenes (8-bromo-3,4,7-trichloro-3,7-dimethyl-1E, 5E-octadiene and 1,8-dibromo-3,4,7-trichloro-3,7-dimethyl-1E, 5E-octadiene) and a cholesterol fraction were isolated from the extract of P. brasiliense prepared in hexane. Algal samples were incubated for 30 minutes with B. jararaca venom, and then tested for lethality; hemorrhagic, edematogenic, hemolytic, coagulant and proteolytic effects. RESULTS: Most of the algal extracts inhibited the toxic effects with different potencies. The DCM extract was the most effective, since it inhibited all types of toxic activity. On the other hand, the HYD extract failed to inhibit any effect. Moreover, the isolated products inhibited proteolysis and protected mice from hemorrhage in 30% of the cases, whereas 8-bromo-3,4,7-trichloro-3,7-dimethyl-1E, 5E-octadiene inhibited 100% and 20% of the hemorrhagic and proteolytic activities, respectively. None of the algal products were toxic to mice. CONCLUSION: Seaweeds may be a promising source of inhibitors against toxic effects caused by B. jararaca envenomation, which may contribute to antivenom treatment.

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