RESUMO
Human immunodeficiency virus (HIV) infection is fast becoming widespread in the world with 37.7 million people living with HIV in 2020. Antiretroviral therapy involving chemical drugs has declined acquired immunodeficiency syndrome (AIDS)-related mortality and improved the life quality of AIDS/HIV sufferers. However, the emergence of drug resistance and side effects are the main obstacles for the long-term use of these chemicals as antiretroviral therapy. Recently, a lot of emphasis is being put on finding naturally occurring drug candidates that show activity against HIV and can be potentially used as antiretroviral therapy. In this study, different medicinal plants, Pistacia khinjuk, Teucrium stocksianum, Uncaria tomentosa, Pistacia integerrima, Trigonella gharuensis, and Artocarpus lakoocha, were explored for their anti-HIV potential. Syncytium and p24 assays were performed to determine antiviral activity, while the MTT assay was used to determine cytotoxicity. Results showed that extracts from all six plants inhibited HIV replication in vitro. Also, extracts from Pistacia khinjuk, Teucrium stocksianum, Uncaria tomentosa, and Pistacia integerrima showed low cytotoxicity with a 50% cytotoxicity concentration value of >200 µM. Results of this study indicate that there is potential in these natural extracts to become candidate drugs to be used as complementary and alternative medicine for HIV infection.
Assuntos
Síndrome da Imunodeficiência Adquirida , Infecções por HIV , HIV-1 , Plantas Medicinais , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêuticoRESUMO
Ribosome-inactivating proteins (RIPs) hydrolyze the N-glycosidic bond and depurinate a specific adenine residue (A-4324 in rat 28S ribosomal RNA, rRNA) in the conserved α-sarcin/ricin loop (α-SRL) of rRNA. In this study, we have purified and characterized lyophyllin, an unconventional RIP from Lyophyllum shimeji, an edible mushroom. The protein resembles peptidase M35 domain of peptidyl-Lys metalloendopeptidases. Nevertheless, protein either from the mushroom or in recombinant form possessed N-glycosidase and protein synthesis inhibitory activities. A homology model of lyophyllin was constructed. It was found that the zinc binding pocket of this protein resembles the catalytic cleft of a classical RIP, with key amino acids that interact with the adenine substrate in the appropriate positions. Mutational studies showed that E122 may play a role in stabilizing the positively charged oxocarbenium ion and H121 for protonating N-3 of adenine. The tyrosine residues Y137 and Y104 may be used for stacking the target adenine ring. This work first shows a protein in the peptidase M35 superfamily based on conserved domain search possessing N-glycosidase activity.
Assuntos
Agaricales/metabolismo , Peptídeo Hidrolases/metabolismo , Proteínas Inativadoras de Ribossomos/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Endorribonucleases/metabolismo , Proteínas Fúngicas/metabolismo , Células HeLa , Células Hep G2 , Humanos , Ligação Proteica/fisiologia , RNA Ribossômico 28S/metabolismo , Ratos , Ricina/metabolismoRESUMO
Due to its multifaceted essential roles in virus replication and extreme genetic fragility, the human immunodeficiency virus type 1 (HIV-1) capsid (CA) protein is a valued therapeutic target. However, CA is as yet unexploited clinically, as there are no antiviral agents that target it currently on the market. To facilitate the identification of potential HIV-1 CA inhibitors, we established a homogeneous time-resolved fluorescence (HTRF) assay to screen for small molecules that target a biologically active and specific binding pocket in the C-terminal domain of HIV-1 CA (CA CTD). The assay, which is based on competition of small molecules for the binding of a known CA inhibitor (CAI) to the CA CTD, exhibited a signal-to-background ratio (S/B)â¯>â¯10 and a Z' valueâ¯>â¯0.9. In a pilot screen of three kinase inhibitor libraries containing 464 compounds, we identified one compound, TX-1918, as a low micromolecular inhibitor of the HIV-1 CA CTD-CAI interaction (IC50â¯=â¯3.81⯵M) that also inhibited viral replication at moderate micromolar concentration (EC50â¯=â¯15.16⯵M) and inhibited CA assembly in vitro. Based on the structure of TX-1918, an additional compound with an antiviral EC50 of 6.57⯵M and cellular cytotoxicity CC50 of 102.55⯵M was obtained from a compound similarity search. Thus, the HTRF-based assay has properties that are suitable for screening large compound libraries to identify novel anti-HIV-1 inhibitors targeting the CA CTD.
Assuntos
Ligação Competitiva , Proteínas do Capsídeo/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos/métodos , Fluorescência , HIV-1/efeitos dos fármacos , Ensaios de Triagem em Larga Escala/métodos , Montagem de Vírus/efeitos dos fármacos , Capsídeo/efeitos dos fármacos , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/metabolismo , Linhagem Celular , Liberação Controlada de Fármacos , Proteínas Recombinantes , Linfócitos T , Replicação Viral/efeitos dos fármacosRESUMO
APOBEC3G is a member of the human cytidine deaminase family that restricts Vif-deficient viruses by being packaged with progeny virions and inducing the G to A mutation during the synthesis of HIV-1 viral DNA when the progeny virus infects new cells. HIV-1 Vif protein resists the activity of A3G by mediating A3G degradation. Phorbol esters are plant-derived organic compounds belonging to the tigliane family of diterpenes and could activate the PKC pathway. In this study, we identified an inhibitor 12-O-tricosanoylphorbol-20-acetate (hop-8), a novel ester of phorbol which was isolated from Ostodes katharinae of the family Euphorbiaceae, that inhibited the replication of wild-type HIV-1 and HIV-2 strains and drug-resistant strains broadly both in C8166 cells and PBMCs with low cytotoxicity and the EC50 values ranged from 0.106 µM to 7.987 µM. One of the main mechanisms of hop-8 is to stimulate A3G expressing in HIV-1 producing cells and upregulate the A3G level in progeny virions, which results in reducing the infectivity of the progeny virus. This novel mechanism of hop-8 inhibition of HIV replication might represents a promising approach for developing new therapeutics for HIV infection.
Assuntos
Fármacos Anti-HIV/farmacologia , Euphorbiaceae/química , HIV-1/efeitos dos fármacos , Interações Hospedeiro-Patógeno , Ésteres de Forbol/farmacologia , Vírion/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Desaminase APOBEC-3G/genética , Desaminase APOBEC-3G/metabolismo , Fármacos Anti-HIV/química , Fármacos Anti-HIV/isolamento & purificação , Linhagem Celular , DNA Viral/antagonistas & inibidores , DNA Viral/biossíntese , Regulação da Expressão Gênica , HIV-1/genética , HIV-1/metabolismo , HIV-2/efeitos dos fármacos , HIV-2/genética , HIV-2/metabolismo , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/virologia , Mutação , Ésteres de Forbol/química , Ésteres de Forbol/isolamento & purificação , Extratos Vegetais/química , Cultura Primária de Células , Proteína Quinase C/genética , Proteína Quinase C/metabolismo , Transdução de Sinais , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Linfócitos T/virologia , Vírion/genética , Vírion/metabolismo , Produtos do Gene vif do Vírus da Imunodeficiência Humana/deficiência , Produtos do Gene vif do Vírus da Imunodeficiência Humana/genéticaRESUMO
Protein-protein interaction between lens epithelium-derived growth factor (LEDGF/p75) and HIV-1 integrase becomes an attractive target for anti-HIV drug development. The blockade of this interaction by small molecules could potentially inhibit HIV-1 replication. These small molecules are termed as LEDGINs; and several newly identified LEDGINs have been reported to significantly reduce HIV-1 replication. Through this project, we have finished the docking screening of the Maybridge database against the p75 binding site of HIV-1 integrase using both DOCK and Autodock Vina software. Finally, we have successfully identified a novel scaffold LEDGINs inhibitor DW-D-5. Its antiviral activities and anticatalytic activity of HIV-1 integrase are similar to other LEDGINs under development. We demonstrated that the combination of DW-D-5 and FDA approved anti-HIV drugs resulted in additive inhibitory effects on HIV-1 replication, indicating that DW-D-5 could be an important component of combination pills for clinic use in HIV treatment.
Assuntos
Fármacos Anti-HIV/farmacologia , Avaliação Pré-Clínica de Medicamentos/métodos , Integrase de HIV/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Fármacos Anti-HIV/metabolismo , Biocatálise , Linhagem Celular , Integrase de HIV/química , HIV-1/efeitos dos fármacos , HIV-1/metabolismo , HIV-1/fisiologia , Peptídeos e Proteínas de Sinalização Intercelular/química , Simulação de Acoplamento Molecular , Ligação Proteica , Conformação Proteica , Software , Replicação Viral/efeitos dos fármacosRESUMO
The search for new molecular constructs that resemble the critical two-metal binding pharmacophore and the halo-substituted phenyl functionality required for HIV-1 integrase (IN) inhibition represents a vibrant area of research within drug discovery. As reported herein, we have modified our recently disclosed 1-[2-(4-fluorophenyl)ethyl]-pyrrole-2,5-dione scaffolds to design 35 novel compounds with improved biological activities against HIV-1. These new compounds show single-digit micromolar antiviral potencies against HIV-1 and low toxicity. Among of them, compound 9g and 15i had potent anti-HIV-1 activities (EC50 < 5 µM) and excellent therapeutic index (TI, CC50/EC50 > 100). These two compounds have potential as lead compounds for further optimization into clinical anti-HIV-1 agents.
Assuntos
Fármacos Anti-HIV , Infecções por HIV/tratamento farmacológico , HIV-1/metabolismo , Pirazóis , Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , Linhagem Celular , Avaliação Pré-Clínica de Medicamentos , Infecções por HIV/metabolismo , Humanos , Pirazóis/síntese química , Pirazóis/química , Pirazóis/farmacologiaRESUMO
BACKGROUND: Small-molecule compounds that inhibit human immunodeficiency virus type 1 (HIV-1) infection can be used not only as drug candidates, but also as reagents to dissect the life cycle of the virus. Thus, it is desirable to have an arsenal of such compounds that inhibit HIV-1 infection by various mechanisms. Until now, only a few small-molecule compounds that inhibit nuclear entry of viral DNA have been documented. RESULTS: We identified a novel, small-molecule compound, SJP-L-5, that inhibits HIV-1 infection. SJP-L-5 is a nitrogen-containing, biphenyl compound whose synthesis was based on the dibenzocyclooctadiene lignan gomisin M2, an anti-HIV bioactive compound isolated from Schisandra micrantha A. C. Smith. SJP-L-5 displayed relatively low cytotoxicity (50% cytoxicity concentrations were greater than 200 µg/ml) and high antiviral activity against a variety of HIV strains (50% effective concentrations (EC50)) of HIV-1 laboratory-adapted strains ranged from 0.16-0.97 µg/ml; EC50s of primary isolates ranged from 1.96-5.33 µg/ml). Analyses of the viral DNA synthesis indicated that SJP-L-5 specifically blocks the entry of the HIV-1 pre-integration complex (PIC) into the nucleus. Further results implicated that SJP-L-5 inhibits the disassembly of HIV-1 particulate capsid in the cytoplasm of the infected cells. CONCLUSIONS: SJP-L-5 is a novel small-molecule compound that inhibits HIV-1 nuclear entry by blocking the disassembly of the viral core.
Assuntos
Fármacos Anti-HIV/farmacologia , DNA Viral/metabolismo , HIV-1/efeitos dos fármacos , HIV-1/fisiologia , Integração Viral/efeitos dos fármacos , Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/isolamento & purificação , Fármacos Anti-HIV/toxicidade , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Schisandra/químicaRESUMO
Eleven triterpene acids including 10 new compounds (kadcoccinic acids A-J, 1-10) were isolated from the stems of Kadsura coccinea. Except for 10, these compounds feature a rearranged lanostane skeleton with a 6/6/5/6 tetracyclic ring system, and compounds 1 and 2 are the first examples of 2,3-seco-6/6/5/6-fused tetracyclic triterpenoids. Their structures were established primarily by spectroscopic and spectrometric methods. Additionally, the absolute configuration of 3 was determined by single-crystal X-ray diffraction. Several of the compounds isolated were tested for their anti-HIV-1 and cytotoxic activities.
Assuntos
Fármacos Anti-HIV/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Kadsura/química , Triterpenos/isolamento & purificação , Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Feminino , HIV-1/efeitos dos fármacos , Células HL-60 , Humanos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Caules de Planta/química , Triterpenos/química , Triterpenos/farmacologiaRESUMO
Ribosome inactivating proteins (RIPs) inhibit protein synthesis by depurinating the large ribosomal RNA and some are found to possess anti-human immunodeficiency virus (HIV) activity. Maize ribosome inactivating protein (RIP) has an internal inactivation loop which is proteolytically removed for full catalytic activity. Here, we showed that the recombinant active maize RIP protected chimeric simian-human immunodeficiency virus (SHIV) 89.6-infected macaque peripheral blood mononuclear cells from lysis ex vivo and transiently reduced plasma viral load in SHIV89.6-infected rhesus macaque model. No evidence of immune dysregulation and other obvious side-effects was found in the treated macaques. Our work demonstrates the potential development of maize RIP as an anti-HIV agent without impeding systemic immune functions.
Assuntos
Antirretrovirais/uso terapêutico , Proteínas Inativadoras de Ribossomos/uso terapêutico , Síndrome de Imunodeficiência Adquirida dos Símios/tratamento farmacológico , Vírus da Imunodeficiência Símia , Carga Viral/efeitos dos fármacos , Zea mays , Animais , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/virologia , Macaca mulatta , Masculino , Proteínas Recombinantes/uso terapêutico , Síndrome de Imunodeficiência Adquirida dos Símios/sangue , Síndrome de Imunodeficiência Adquirida dos Símios/virologiaRESUMO
The interaction between HIV-1 integrase and LEDGF/P75 has been validated as a target for anti-HIV drug development. Based on the crystal structure of integrase in complex with LEDGF/P75, a library containing 80 thousand natural compounds was filtered with virtual screening. 11 hits were selected for cell based assays. One compound, 3-(1,3-benzothiazol-2-yl)-8-{[bis(2-hydroxyethyl)amino]methyl}-7-hydroxy-2H-chromen-2-one (D719) inhibited integrase nuclear translocation in cell imaging. The binding mode of D719 was analyzed with molecular simulation. The anti-HIV activity of D719 was assayed by measuring the p24 antigen production in acute infection. The structure characteristics of D719 may provide valuable information for integrase inhibitor design.
Assuntos
Benzotiazóis/química , Cumarínicos/química , Inibidores de Integrase de HIV/química , HIV-1/efeitos dos fármacos , Modelos Moleculares , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Benzotiazóis/farmacologia , Domínio Catalítico , Simulação por Computador , Cumarínicos/farmacologia , Avaliação Pré-Clínica de Medicamentos , Proteína do Núcleo p24 do HIV/biossíntese , Integrase de HIV/química , Inibidores de Integrase de HIV/farmacologia , HIV-1/enzimologia , Células HeLa , Humanos , Ligação ProteicaRESUMO
AIM: To evaluate the anti-HIV activity and mechanism of action of wikstroelide M, a daphnane diterpene from Daphne acutiloba Rehder (Thymelaeaceae). METHODS: The anti-HIV activities of wikstroelide M against different HIV strains were evaluated by cytopathic effect assay and p24 quantification assay with ELISA. The inhibitory effect of wikstroelide M on HIV reverse transcription was analyzed by real-time PCR and ELISA. The effect of wikstroelide M on HIV-1 integrase nuclear translocation was observed with a cell-based imaging assay. The effect of wikstroelide M on LEDGF/p75-IN interaction was assayed by molecular docking. RESULTS: Wikstroelide M potently inhibited different HIV-1 strains, including HIV-1IIIB, HIV-1A17, and HIV-19495, induced a cytopathic effect, with EC50 values ranging from 3.81 to 15.65 ng·mL⻹. Wikstroelide M also had high inhibitory activities against HIV-2ROD and HIV-2CBL-20-induced cytopathic effects with EC50 values of 18.88 and 31.90 ng·mL⻹. The inhibitory activities of wikstroelide M on the three HIV-1 strains were further confirmed by p24 quantification assay, with EC50 values ranging from 15.16 to 35.57 ng·mL⻹. Wikstroelide M also potently inhibited HIV-1IIIB induced cytolysis in MT-4 cells, with an EC50 value of 9.60 ng·mL⻹. The mechanistic assay showed that wikstroelide M targeted HIV-1 reverse transcriptase and nuclear translocation of integrase through disrupting the interaction between integrase and LEDGF/p75. CONCLUSION: Wikstroelide M may be a potent HIV-1 and HIV-2 inhibitor, the mechanisms of action may include inhibition of reverse trascriptase activity and inhibition of integrase nuclear translocation through disrupting the interaction between integrase and LEDGF/p75.
Assuntos
Fármacos Anti-HIV/farmacologia , Daphne/química , Diterpenos/farmacologia , Integrase de HIV/metabolismo , Transcriptase Reversa do HIV/antagonistas & inibidores , HIV-1/efeitos dos fármacos , HIV-2/efeitos dos fármacos , Extratos Vegetais/farmacologia , Fármacos Anti-HIV/uso terapêutico , Linhagem Celular , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Inibidores de Integrase de HIV/farmacologia , Inibidores de Integrase de HIV/uso terapêutico , HIV-1/enzimologia , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Fitoterapia , Extratos Vegetais/uso terapêutico , Integração Viral/efeitos dos fármacos , Replicação Viral/efeitos dos fármacosRESUMO
Three tigliane-type diterpenoids named excoecafolins A-C and two daphnane-type diterpenoids named excoecafolins D and E, together with 13 known compounds, were isolated from the EtOAc extract of Excoecaria acerifolia Didr. Their structures were elucidated through the analysis of the spectroscopic data. The anti-HIV-1 activity evaluation of five of these compounds showed that four possessed moderate anti-HIV-1 activities with EC50 0.258, 0.036, 0.046, and 0.978 µM, SI >1,836.9, 431.1, 298.7, and >503.7, respectively. Additionally, the chemotaxonomic issue of the affinity correlation between Thymelaeceae and Euphorbiaceae is discussed based on the isolates.
Assuntos
Fármacos Anti-HIV/isolamento & purificação , Diterpenos/isolamento & purificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Euphorbiaceae/química , HIV-1/efeitos dos fármacos , Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , Diterpenos/química , Diterpenos/farmacologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Caules de Planta/química , Plantas MedicinaisRESUMO
Two new triterpenoids, schisphendilactone A and B (1 and 2), together with three known triterpenoids, were isolated from the stems of Schisandra sphenanthera. Their structures were elucidated by spectroscopic methods, and the absolute configuration of 1 was determined by single-crystal X-ray diffraction. Compound 2 showed moderate inhibitory activity against SW480 cancer cell line, and compound 5 exhibited promising anti-HIV-1 activity with EC50 value of 0.52 µg ml(-1) and therapeutic index value of 117.12.
Assuntos
Fármacos Anti-HIV , Antineoplásicos Fitogênicos , Medicamentos de Ervas Chinesas , Schisandra/química , Triterpenos , Fármacos Anti-HIV/isolamento & purificação , Fármacos Anti-HIV/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cristalografia por Raios X , Efeito Citopatogênico Viral , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Concentração Inibidora 50 , Estrutura Molecular , Caules de Planta/química , Estereoisomerismo , Triterpenos/isolamento & purificação , Triterpenos/farmacologiaRESUMO
Three new triterpenoids, kadcotriones A-C (1-3), together with the biogenetically related lanostane-type triterpenoid (4), were isolated from Kadsura coccinea. Compound 1 features a 12,14ß-dimethyl 6/6/6-fused tricyclic skeleton, while 2 and 3 are characterized by a 6/6/5-ring system. Their structures were determined by NMR and electronic circular dichroism spectroscopic methods. Compounds 2 and 4 exhibited anti-HIV-1 activities with EC50 values of 30.29 and 54.81 µM, respectively.
Assuntos
Fármacos Anti-HIV/isolamento & purificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Kadsura/química , Triterpenos/isolamento & purificação , Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , Dicroísmo Circular , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , HIV-1/efeitos dos fármacos , Estrutura Molecular , Caules de Planta/química , Triterpenos/química , Triterpenos/farmacologiaRESUMO
Sixteen daphnane diterpenoids, trigothysoids A-P, along with 15 known ones, were isolated from the methanol extract of the twigs and leaves of Trigonostemon thyrsoideum. Their structures were established by extensive spectroscopic techniques, including 2D NMR spectroscopy and mass spectrometry. The anti-HIV-1 activity of the compounds was also evaluated in vitro, and five compounds demonstrated potent anti-HIV-1 activity, with EC50 values of 0.015-0.001 nM and TI values of 1618-17,619.
Assuntos
Fármacos Anti-HIV/isolamento & purificação , Fármacos Anti-HIV/farmacologia , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Euphorbiaceae/química , Fármacos Anti-HIV/química , Diterpenos/química , Medicamentos de Ervas Chinesas/química , HIV-1/efeitos dos fármacos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Folhas de Planta , Caules de Planta/químicaRESUMO
Five new diterpenoids named excocarinols A-E (1-5) including three pimaranes, one cleistanthane, and one nor-beyerane, together with nine known compounds, were isolated from the EtOAc extract of the Chinese ethnodrug Gua-jing-ban (Excoecaria acerifolia Didr.). Their structures were elucidated by the analysis of spectroscopic data including 1D, 2D NMR and HR-MS. The anti-HIV-1 bioassay on the diterpenoids showed that excocarinol A (1) exhibited moderate anti-HIV-1 activity with EC50 5.58 µM and SI (Selection Index) over 112.71.
Assuntos
Fármacos Anti-HIV/farmacologia , Diterpenos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Euphorbiaceae/química , HIV-1/efeitos dos fármacos , Abietanos/química , Abietanos/isolamento & purificação , Abietanos/farmacologia , Fármacos Anti-HIV/química , Fármacos Anti-HIV/isolamento & purificação , Diterpenos/química , Diterpenos/isolamento & purificação , Medicamentos de Ervas Chinesas/química , Estrutura MolecularRESUMO
Three new unusual 23-spirocholestane derivatives, ypsilanogenin (1), ypsilanogenin 3-O-ß-D-glucopyranoside (2), and 4'-acetylypsilanogenin 3-O-ß-D-glucopyranoside (3), were isolated from the whole plants of Ypsilandra thibetica. The structures of compounds 1-3 were deduced by spectroscopic and chemical methods, and the structure of 1 was further confirmed by a single-crystal diffraction analysis. All isolates were evaluated for their inhibitory activities against HIV-1.
Assuntos
Fármacos Anti-HIV/farmacologia , Glicosídeos/farmacologia , Liliaceae/química , Fármacos Anti-HIV/química , Fármacos Anti-HIV/isolamento & purificação , Colestanos/química , Colestanos/isolamento & purificação , Colestanos/farmacologia , Cristalografia por Raios X , Glicosídeos/química , Glicosídeos/isolamento & purificação , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Plantas Medicinais , Saponinas/química , Saponinas/isolamento & purificação , Saponinas/farmacologia , Compostos de Espiro/química , Compostos de Espiro/isolamento & purificação , Compostos de Espiro/farmacologiaRESUMO
Three new dibenzocyclooctadiene lignans, marlignans M-O (1-3), together two known ones, were isolated from the leaves and stems of Schisandra wilsoniana. The structures of 1-3 were elucidated by spectroscopic methods, including extensive 1D- and 2D-NMR techniques. Compound 2 showed anti-HIV-1 activity with an EC50 value of 5.82 microg/mL and a therapeutic index (TI) of more than 12.8. Compound 3 showed obvious bioactivity in inhibiting Epstein-Barr virus early antigen (EBV-EA) activation.
Assuntos
Fármacos Anti-HIV/isolamento & purificação , HIV-1/efeitos dos fármacos , Lignanas/isolamento & purificação , Schisandra/química , Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , Antígenos Virais/metabolismo , Lignanas/química , Lignanas/farmacologia , Espectroscopia de Ressonância Magnética , Folhas de Planta/química , Caules de Planta/químicaRESUMO
Seven new unusual dibenzocyclooctadiene lignans, neglignans A-G (1-7), together with 16 known dibenzocyclooctadiene lignans, were isolated from the stems of Schisandra neglecta. Compounds 1 and 2 are the first dibenzocyclooctadiene lignans bearing a carboxyl group at C-4, and compounds 3 and 4 are the first 7,8-seco-dibenzocyclooctadiene lignans found from Nature. The new compounds (1-7) and several of the known compounds were evaluated for their anti-HIV activity and cytotoxicity. Compounds 2 and 6 showed anti-HIV-1 activities with therapeutic index values greater than 50, and compound 4 showed cytotoxicity against the NB4 and SHSY5Y cancer cell lines with IC50 values of 2.9 and 3.3 µM, respectively.
Assuntos
Fármacos Anti-HIV/isolamento & purificação , Fármacos Anti-HIV/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Ciclo-Octanos/isolamento & purificação , Ciclo-Octanos/farmacologia , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Lignanas/isolamento & purificação , Lignanas/farmacologia , Schisandra/química , Fármacos Anti-HIV/química , Antineoplásicos Fitogênicos/química , Ciclo-Octanos/química , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , HIV-1/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Lignanas/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Caules de Planta/químicaRESUMO
Six new lignans, schisphenlignans F-K (1-6), together with ten known ones, were isolated from the leaves and stems of Schisandra sphenanthera. Their structures were elucidated on the basis of spectroscopic methods, including extensive NMR, MS and CD spectra. In addition, some compounds were tested for their acute activity on insulin sensitivity in 3T3-L1 differentiated adipocytes and anti-HIV-1 activity.