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

Inhibition of HIV-1 replication in human primary cells by a Dolabellane Diterpene isolated from the marine Algae Dictyota pfaffii

Submitted by Sandra Infurna ([email protected]) on 2020-01-03T13:14:27Z No. of bitstreams: 1 LuizRR_CasteloBranco_etal_IOC_2006.pdf: 88033 bytes, checksum: 1c07f1773a945cdb2a8eece147efc60a (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2020-01-03T13:29:06Z (GMT) No. of bitstreams: 1 LuizRR_CasteloBranco_etal_IOC_2006.pdf: 88033 bytes, checksum: 1c07f1773a945cdb2a8eece147efc60a (MD5)Made available in DSpace on 2020-01-03T13:29:06Z (GMT). No. of bitstreams: 1 LuizRR_CasteloBranco_etal_IOC_2006.pdf: 88033 bytes, checksum: 1c07f1773a945cdb2a8eece147efc60a (MD5) Previous issue date: 2006Universidade Federal Fluminense. Departamento de Biologia Celular e Molecular. Laboratório de Virologia Molecular. Niterói, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Prof. Paulo de Góes. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Imunologia. Laboratório de Imunologia Clínica. Rio de Janeiro, RJ, Brasil.Universidade Federal Fluminense. Departamento de Biologia Marinha. Laboratório de Biologia Marinha. Niteói, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Imunologia. Laboratório de Imunologia Clínica. Rio de Janeiro, RJ, Brasil.Universidade Federal Fluminense. Departamento de Biologia Celular e Molecular. Laboratório de Virologia Molecular. Niterói, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Imunologia. Laboratório de Imunologia Clínica. Rio de Janeiro, RJ, Brasil.We describe in this paper that the dolabellane diterpene 8,10,18-trihydroxy-2,6-dolabelladiene (3), isolated from the marine algae Dictyota pfaffii, inhibits the HIV-1 infection in human primary cells and tumor cell lines. We initially observed that compound 3 inhibited the activity of a purified HIV-1 enzyme reverse transcriptase (RT) in a dose-dependent manner, with an IC (50) value of 16.5 +/- 4.3 microM. Next, we found that compound 3 inhibited HIV-1 infection by an R5-tropic isolate in peripheral blood mononuclear cells (PBMCs) in a dose-dependent manner with an EC (50) value of 8.4 +/- 2.8 microM. The replication of HIV-1 isolates presenting distinct tropism for chemokine receptors was also inhibited, as analyzed in PBMCs or U87 cells infected with R5-, X4- or R5X4-tropic isolates. Likewise, compound 3 blocked HIV-1 infection in macrophages by R5 and R5X4 viruses in a dose-dependent manner with EC (50) values of 1.7 +/- 0.6 microM and 1.85 +/- 0.75 microM, respectively. Compound 3 sustained antiretroviral activity even when added to HIV-1-infected Sup-T1 cells at 12 h after infection, suggesting that, as well as inhibiting HIV-1 RT, it also blocks HIV-1 replication at a post transcriptional step. Our results support further investigations on compound 3 pharmacokinetics and we propose that this diterpene could be considered as a potential compound for HIV-1 therapy

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

Anti-HIV-1 activity of the Iboga alkaloid congener 18-methoxycoronaridine.

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2014-08-05T17:35:17Z No. of bitstreams: 1 Silva EM Anti-HIV....pdf: 197976 bytes, checksum: 572839340f28382b8e5a79474f73930c (MD5)Made available in DSpace on 2014-08-05T17:35:18Z (GMT). No. of bitstreams: 1 Silva EM Anti-HIV....pdf: 197976 bytes, checksum: 572839340f28382b8e5a79474f73930c (MD5) Previous issue date: 2004Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório Avançado de Saúde Pública. Salvador, BA, BrasilUniversidade Federal Fluminense. Laboratório de Virologia Molecular. Departamento de Biologia Celular e Molecular. Rio de Janeiro, RJ, Brasil / Instituto Oswaldo Cruz. Laboratório de Imunologia Clínica. Departamento de Imunologia. Rio de Janeiro, RJ, BrasilUniversidade Federal Fluminense. Laboratório de Virologia Molecular. Departamento de Biologia Celular e Molecular. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório Avançado de Saúde Pública. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Fundação Bahiana para o Desenvolvimento das Ciências. Salvador, BA, BrasilUniversidade Federal do Rio de Janeiro. Instituto de Microbiologia. Departamento de Imunologia. Rio de Janeiro, RJ, BrasilUniversity of Vermont. Department of Chemistry. Burlington, VT, USAInstituto Oswaldo Cruz. Laboratório de Imunologia Clínica. Departamento de Imunologia. Rio de Janeiro, RJ, BrasilThe Iboga alkaloid congener 18-methoxycoronaridine (18-MC) exhibits in vitro leishmanicidal and in vivo anti-addiction properties. In this paper, we describe that 18-MC inhibits HIV-1 infection in human peripheral blood mononuclear cells (PBMCs) and monocyte-derived macrophages. We found that 18-MC inhibits the replication of primary isolates of HIV-1 in a dose-dependent manner, regardless of the preferential chemokine receptor usage of the isolates, at non-cell-toxic concentrations. The antiretroviral activity of 18-MC resulted in EC (50) values of 22.5 +/- 4.7 microM and 23 +/- 4.5 microM for R5 and X4 isolates, respectively, in PBMCs, and a therapeutic index (TI) of 14.5. Similar findings were observed for inhibition of HIV-1 replication in macrophages: EC (50) equal to 12.8 +/- 5 microM and 9.5 +/- 3 microM for an R5 virus after 14 and 21 days of infection, respectively, with TI equal to 25.6 and 34.5. 18-MC moderately inhibits the HIV-1 enzyme reverse transcriptase (IC (50) = 69.4 microM), which at least partially explains its antiretroviral activity

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