Dolabellane diterpenes from the Caribbean soft corals Eunicea laciniata and Eunicea asperula and determination of their anti HSV-1 activity

Dolabellane diterpenes have considerable antiviral activity, most studies have been focused towards compounds isolated from Dictyota brown algae. Although soft corals are also a significant source of these diterpenes, their antiviral potential has not been studied in detail. With the aim of assessing the biological activity of marine sources, we evaluated the dolabellane content in the soft corals Eunicea laciniata and E. asperula collected in Santa Marta, Colombian Caribbean. Dolabellanes 1-6 were isolated from E. laciniata while compounds 2, 4 and 5 were isolated from E. asperula. All compounds were identified by NMR, GC-EIMS, optical rotation and comparison with previously reported dolabellanes. GC-EIMS analyses showed that dolabellatrienone (2) transforms into compounds 4 and 5 as oxidation products upon prolonged storage; however, those compounds were also naturally present in the extract of the studied organisms. Pure dolabellanes were tested in vitro in antiviral assays against HSV-1. Compound 6 inhibited virus replication in infected cells (73.7% of inhibition at 50 μM) without cytotoxic effect (CC50 = 959), showing similar activity to the positive control Acyclovir®. Thus, compound 6 is an interesting candidate for further studies of dolabellanes as antivirals.Los dolabellanos son diterpenos con importante actividad antiviral, la mayor parte de los estudios se han realizado con compuestos aislados de algas pardas del género Dictyota. Los corales blandos son también una importante fuente de dolabellanos, pero el potencial antiviral de éstos ha sido muy poco estudiado. Como parte de nuestra búsqueda de compuestos bioactivos a partir de fuentes marinas, se llevó a cabo el estudio químico de los dolabellanos presentes en los octocorales Eunicea laciniata y Eunicea asperula, recolectados en Santa Marta, Caribe colombiano. Los dolabellanos 1-6 fueron aislados del octocoral E. laciniata mientras que en E. asperula se encontraron los compuestos 2, 4 y 5. La elucidación estructural se llevó a cabo mediante experimentos de RMN, espectrometría de masas, rotación óptica y posterior comparación con reportes previos en la literatura. El análisis por CG-EM evidenció que la dolabellatrienona (2) se puede transformar en los compuestos 4 y 5 como producto del almacenamiento prolongado, no obstante, tales compuestos también estuvieron presentes en los extractos de los organismos estudiados. El compuesto 6 inhibió la replicación del VHS-1 (73,7% de inhibición en células infectadas a una concentración de 50 μM) sin efecto citotóxico (CC50 = 959), mostrando una citotoxicidad similar al Aciclovir®, un control positivo, por lo cual se perfila como un candidato para la realización de estudios adicionales sobre el potencial de los dolabellanos como agentes antivirales

Dolabelladienols A–C, New Diterpenes Isolated from Brazilian Brown Alga Dictyota pfaffii

[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.Brasil. Conselho Nacional de Desenvolvimento Científico e Tecnológico; 490425/2010-0Brasil. Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro ; E-26/103.176/2011Ministerio de Economia y Competitividad; AGL2012-12266-C0

Human Papillomavirus Infection and Cervical Cancer in Brazil: a Retrospective Study

Two hundred and thirty paraffin-embedded biopsies obtained from female cervical lesions were tested for the presence of human papillomavirus (HPV) types 6/11,16/18 and 31/33/35 DNA using non-isotopic in situ hybridization. Specimens were classified according to the Bethesda System in low grade squamous intraepithelial lesion (LSIL), high grade SIL (HSIL) and squamous cell carcinoma (SCC). HPV prevalence ranged from 92.5% in LSIL to 68.5% in SCC. Benign types were prevalent in LSILs while oncogenic types infected predominantly HSILs and SCC. HPV infection showed to be age-dependent, but no significant relation to race has been detected. Patients were analyzed through a five-year period: 20.7% of the lesions spontaneously regressed while 48.9% persisted and 30.4% progressed to carcinoma. Patients submitted to treatment showed a 19.4% recurrence rate. High risk types were present in 78.6% (CrudeOR 13.8, P=0.0003) of the progressive lesions, and in 73.7% of the recurrent SILs (COR 19.3, P=0.0000001). Possible co-factors have also been evaluated: history of other sexually transmitted diseases showed to be positively related either to progression (Adjusted OR 13.0, P=0.0002) or to recurrence (AOR 17.2, P=0.0002) while oral contraceptive use and tobacco smoking were not significantly related to them (P>0.1). Association of two or more co-factors also proved to be related to both progression and recurrence, indicating that they may interact with HPV infection in order to increase the risk of developing malignant lesions

Dolabellanos de los octocorales caribeños Eunicea laciniata y Eunicea asperula y determinación de su actividad anti VHS-1

Los dolabellanos son diterpenos con importante actividad antiviral, la mayor parte de los estudios se han realizado con compuestos aislados de algas pardas del género Dictyota. Los corales blandos son también una importante fuente de dolabellanos, pero el potencial antiviral de éstos ha sido muy poco estudiado. Como parte de nuestra búsqueda de compuestos bioactivos a partir de fuentes marinas, se llevó a cabo el estudio químico de los dolabellanos presentes en los octocorales Eunicea laciniata y Eunicea asperula, recolectados en Santa Marta, Caribe colombiano. Los dolabellanos 1-6 fueron aislados del octocoral E. laciniata mientras que en E. asperula se encontraron los compuestos 2, 4 y 5. La elucidación estructural se llevó a cabo mediante experimentos de RMN, espectrometría de masas, rotación óptica y posterior comparación con reportes previos en la literatura. El análisis por CG-EM evidenció que la dolabellatrienona (2) se puede transformar en los compuestos 4 y 5 como producto del almacenamiento prolongado, no obstante, tales compuestos también estuvieron presentes en los extractos de los organismos estudiados. El compuesto 6 inhibió la replicación del VHS-1 (73,7% de inhibición en células infectadas a una concentración de 50 μM) sin efecto citotóxico (CC50 = 959), mostrando una citotoxicidad similar al Aciclovir®, un control positivo, por lo cual se perfila como un candidato para la realización de estudios adicionales sobre el potencial de los dolabellanos como agentes antivirales

Anti-HIV-1 activity in human primary cells and Anti-HIV- 1 RT inhibitory activity of extracts from the red seaweed Acanthophora spicifera

Submitted by Sandra Infurna ([email protected]) on 2017-12-21T15:53:18Z No. of bitstreams: 1 claudiocesar_santos_etal_IOC_2016.pdf: 510025 bytes, checksum: ad479082bf4c7e7c22f0398b90231411 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2017-12-21T16:04:33Z (GMT) No. of bitstreams: 1 claudiocesar_santos_etal_IOC_2016.pdf: 510025 bytes, checksum: ad479082bf4c7e7c22f0398b90231411 (MD5)Made available in DSpace on 2017-12-21T16:04:33Z (GMT). No. of bitstreams: 1 claudiocesar_santos_etal_IOC_2016.pdf: 510025 bytes, checksum: ad479082bf4c7e7c22f0398b90231411 (MD5) Previous issue date: 2016Universidade Federal Fluminense. Instituto de Biologia. Departamento de Biologia Marinha. Niterói, RJ, Brasil / Universidade Federal Fluminense. Instituto de Biologia. Departamento de Biologia Celular e Molecular. Niterói, RJ, Brasil.Universidade Federal Fluminense. Instituto de Biologia. Departamento de Biologia Celular e Molecular. Niterói, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Clínica. Rio de Janeiro, RJ. BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ. Brasil.Universidade Federal Fluminense. Instituto de Biologia. Departamento de Biologia Marinha. Niterói, RJ, Brasil.Universidade Federal Fluminense. Instituto de Biologia. Departamento de Biologia Celular e Molecular. Niterói, RJ, Brasil.Universidade Federal Fluminense. Instituto de Biologia. Departamento de Biologia Marinha. Niterói, RJ, Brasil.First generation drugs such as zidovudine have been extensively used in clinical practice, resulting in the development of HIV resistance to these nucleoside analogs. Several studies have demonstrated the effective anti-HIV activity of natural products derived from seaweeds, suggesting promising sources of substances for the development of novel antiviral drugs. In this paper, the antiviral effect of extracts from the red seaweed Acanthophora spicifera on HIV-1 replication was evaluated in vitro. Peripheral blood mononuclear cells obtained using the Ficoll-Hypaque gradient were used for cytotoxicity and antiviral activity testing. The dichloromethane extracts, ethyl acetate, acetone, and methanol were found to have CC50 values of 31±7.4, 45±11, 38±3.5, and 179±25 μg/mL, respectively. With the control, the extract prepared in ethyl acetate inhibited approximately 60% of the viral load, which is the best result among the extracts. This same extract showed an IC50 value of 33.17±4.84 μg/mL for the reverse transcriptase. The EtOAc extract from A. spicifera showed to be an efficient HIV antiviral due to its phenolic compounds, as evaluated by nuclear magnetic resonance

Marine natural seaweed products as potential antiviral drugs against Bovine viral diarrhea virus

Bovine viral diarrhea virus (BVDV) is an etiologic agent that causes important economic losses in the world. It is endemic in cattle herds in most parts of the world. The purpose of this study was to evaluate the in vitro cytotoxic effect and antiviral properties of several marine natural products obtained from seaweeds: the indole alkaloid caulerpin (CAV, 1) and three diterpenes: 6-hydroxydichotoma-3,14-diene-1,17-dial (DA, 2), 10,18-diacetoxy-8-hydroxy-2,6-dolabelladiene (DB1, 3) and 8,10,18-trihydroxy-2,6-dolabelladiene (DB3, 4). The screening to evaluate the cytotoxicity of compounds did not show toxic effects to MDBK cells. The antiviral activity of the compounds was measured by the inhibition of the cytopathic effect on infected cells by plaque assay (PA) and EC50 values were calculated for CAV (EC=2,0± 5.8), DA (EC 2,8± 7.7), DB1 (EC 2,0±9.7), and DB3 (EC 2,3±7.4). Acyclovir (EC50 322± 5.9) was used in all experiments as the control standard. Although the results of the antiviral activity suggest that all compounds are promising as antiviral agents against BVDV, the Selectivity Index suggests that DB1 is the safest of the compounds tested

Thieno[2,3-b]pyridine derivatives: a new class of antiviral drugs against Mayaro virus

Mayaro virus (MAYV) is an arthropod-borne virus and a member of the family Togaviridae, genus Alphavirus. Its infection leads to an acute illness accompanied by long-lasting arthralgia. To date, there are no antiviral drugs or vaccines against infection with MAYV and resources for the prevention or treatment of other alphaviruses are very limited. MAYV has served as a model to study the antiviral potential of several substances on alphavirus replication. In this work we evaluated the antiviral effect of seven new derivatives of thieno[2,3-b]pyridine against MAYV replication in a mammalian cell line. All derivatives were able to reduce viral production effectively at concentrations that were non-toxic for Vero cells. Molecular modeling assays predicted low toxicity risk and good oral bioavailability of the substances in humans. One of the molecules, selected for further study, demonstrated a strong anti-MAYV effect at early stages of replication, as it protected pre-treated cells and also during the late stages, affecting virus morphogenesis. This study is the first to demonstrate the antiviral effect of thienopyridine derivatives on MAYV replication in vitro, suggesting the potential application of these substances as antiviral molecules against alphaviruses. Additional in vivo research will be needed to expand the putative therapeutic applications.Fil: Amorim, Raquel. Universidade Federal do Rio de Janeiro; BrasilFil: Meneses, Marcelo Damião Ferreira de. Universidade Federal do Rio de Janeiro; BrasilFil: Borges, Julio Cesar. Instituto Federal de Educação, Ciência e Tecnologia do Rio de Janeiro; BrasilFil: Pinheiro, Luiz Carlos da Silva. Universidade Federal do Rio de Janeiro; BrasilFil: Caldas, Lucio Ayres. Universidade Federal do Rio de Janeiro; BrasilFil: Cirne Santos, Claudio Cesar. Universidade Federal do Rio de Janeiro; BrasilFil: Mello, Marcos Vinícius Palmeira de. Universidade Federal Fluminense; BrasilFil: Souza, Alessandra Mendonça Teles de. Universidade Federal do Rio de Janeiro; BrasilFil: Castro, Helena Carla. Universidade Federal Fluminense; BrasilFil: Paixão, Izabel Christina Nunes de Palmer. Universidade Federal Fluminense; BrasilFil: Campos, Renata de Mendonça. Universidade Federal do Rio de Janeiro; BrasilFil: Bergmann, Ingrid Evelyn. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología ; ArgentinaFil: Malirat, Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología ; ArgentinaFil: Bernardino, Alice Maria Rolim. Universidade Federal Fluminense; BrasilFil: Rebello, Moacyr Alcoforado. Universidade Federal do Rio de Janeiro; BrasilFil: Fernandes Ferreira, Davis. Universidade Federal do Rio de Janeiro; Brasi