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Carboxymethylated derivatives of pullulan (PU) were synthesized and evaluated as coating for the postharvest preservation of blueberries. Carboxymethylpullulan was obtained by etherification reaction with the substitution degrees of 0.52, 0.34, and 0.26 for CMP1, CMP2, and CMP3 respectively. Infrared spectroscopy and nuclear magnetic resonance results showed characteristic signals of the carbonyl group belonging to the carboxymethyl group. Thermal analysis showed that CMP1, CMP2, and CMP3 derivatives presented thermal stability values of 209.91 C, 214.73 C, and 225.52 °C, respectively, and were lower with respect to PU with Td of 238.84 °C. Furthermore, an increase in the glass transition temperature due to carboxymethylation was determined. The chemical modification decreased the contact angle with respect to PU (71.34°) with values for CMP1, CMP2, and CMP3 of 39.89°, 53.72° and 60.61°, respectively. The carboxymethylation also increased the water vapor permeability and mechanical properties of the films. In addition, it was found that the CMP molecules affected the optical properties. The application of CMP-based coatings reduced the mass loss and ripening rate of blueberries compared to native pullulan, therefore, packaging from CMP molecules could be used as a coating capable of delaying ripening and extending the shelf life of fruits.
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Embalaje de Alimentos , Glucanos , Glucanos/química , Arándanos Azules (Planta)/química , Conservación de Alimentos/métodos , Permeabilidad , Vapor , Frutas/químicaRESUMEN
Although the disease caused by chikungunya virus (CHIKV) is of great interest to public health organizations around the world, there are still no authorized antivirals for its treatment. Previously, dihalogenated anti-CHIKV compounds derived from L-tyrosine (dH-Y) were identified as being effective against in vitro infection by this virus, so the objective of this study was to determine the mechanisms of its antiviral action. Six dH-Y compounds (C1 to C6) dihalogenated with bromine or chlorine and modified in their amino groups were evaluated by different in vitro antiviral strategies and in silico tools. When the cells were exposed before infection, all compounds decreased the expression of viral proteins; only C4, C5 and C6 inhibited the genome; and C1, C2 and C3 inhibited infectious viral particles (IVPs). Furthermore, C1 and C3 reduce adhesion, while C2 and C3 reduce internalization, which could be related to the in silico interaction with the fusion peptide of the E1 viral protein. Only C3, C4, C5 and C6 inhibited IVPs when the cells were exposed after infection, and their effect occurred in late stages after viral translation and replication, such as assembly, and not during budding. In summary, the structural changes of these compounds determine their mechanism of action. Additionally, C3 was the only compound that inhibited CHIKV infection at different stages of the replicative cycle, making it a compound of interest for conversion as a potential drug.
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Antivirales , Fiebre Chikungunya , Virus Chikungunya , Tirosina , Replicación Viral , Virus Chikungunya/efectos de los fármacos , Virus Chikungunya/fisiología , Tirosina/farmacología , Tirosina/análogos & derivados , Tirosina/metabolismo , Tirosina/química , Antivirales/farmacología , Antivirales/química , Fiebre Chikungunya/tratamiento farmacológico , Fiebre Chikungunya/virología , Animales , Replicación Viral/efectos de los fármacos , Chlorocebus aethiops , Células Vero , Humanos , Internalización del Virus/efectos de los fármacos , Proteínas Virales/metabolismoRESUMEN
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a betacoronavirus responsible for the COVID-19 pandemic, causing respiratory disorders, and even death in some individuals, if not appropriately treated in time. To face the pandemic, preventive measures have been taken against contagions and the application of vaccines to prevent severe disease and death cases. For the COVID-19 treatment, antiviral, antiparasitic, anticoagulant and other drugs have been reused due to limited specific medicaments for the disease. Drug repurposing is an emerging strategy with therapies that have already tested safe in humans. One promising alternative for systematic experimental screening of a vast pool of compounds is computational drug repurposing (in silico assay). Using these tools, new uses for approved drugs such as chloroquine, hydroxychloroquine, ivermectin, zidovudine, ribavirin, lamivudine, remdesivir, lopinavir and tenofovir/emtricitabine have been conducted, showing effectiveness in vitro and in silico against SARS-CoV-2 and some of these, also in clinical trials. Additionally, therapeutic options have been sought in natural products (terpenoids, alkaloids, saponins and phenolics) with promising in vitro and in silico results for use in COVID-19 disease. Among these, the most studied are resveratrol, quercetin, hesperidin, curcumin, myricetin and betulinic acid, which were proposed as SARS-CoV-2 inhibitors. Among the drugs reused to control the SARS-CoV2, better results have been observed for remdesivir in hospitalized patients and outpatients. Regarding natural products, resveratrol, curcumin, and quercetin have demonstrated in vitro antiviral activity against SARS-CoV-2 and in vivo, a nebulized formulation has demonstrated to alleviate the respiratory symptoms of COVID-19. This review shows the evidence of drug repurposing efficacy and the potential use of natural products as a treatment for COVID-19. For this, a search was carried out in PubMed, SciELO and ScienceDirect databases for articles about drugs approved or under study and natural compounds recognized for their antiviral activity against SARS-CoV-2.
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The Colombian Chocó is known for its rich biodiversity and to harbor plant species that are under-explored, including the genus Sloanea. This study aimed to analyze the chemical composition of derivatized ethanolic extracts from S. chocoana and S. pittieriana using BSTFA and TMCS through GC-MS, and to assess cell viability of immortalized human non-tumorigenic keratinocytes (HaCaT) and periodontal ligament fibroblast cells using crude extracts through MTS assay. Antioxidant and photoprotective properties were determined using DPPH assay and spectrophotometry. Antifungal activity of extracts against Candida species was developed following the CLSI standard M27, 4th ed. The sun protective factor (SPF) and UVA/UVB ratio values were calculated using the Mansur equation and the Boots star rating system. The critical wavelength (λc) was determined by calculating the integrated optical density curve's area. The transmission of erythema and pigmentation was calculated through equations that use constants to calculate the flux of erythema and pigmentation. The GC-MS analysis identified 37 compounds for S. chocoana and 38 for S. pittieriana, including alkaloids, triterpenoids, and polyphenolics, among others. Both extracts exhibited proliferative effects on periodontal ligament fibroblasts, did not affect the viability of HaCaT cells, and showed excellent antioxidant activities (46.1% and 43.7%). Relevant antifungal activity was observed with S. pittieriana extract against Candida albicans (GM-MIC: 4 µg/mL), followed by C. auris and C. glabrata (GM-MIC: 32 µg/mL), while S. chocoana extract was active against C. albicans and C. glabrata (GM-MIC: 16 and 32 µg/mL, respectively). High SPF values (31.0 and 30.0), λc (393.98 and 337.81 nm), UVA/UVB ratio (1.5 and 1.2), and low percentage of transmission of erythema and pigmentation were determined for S. chocoana and S. pittieriana, respectively. Results showed that species of Sloanea constitute a promising alternative as ingredients for developing skincare products, and exhaustive studies are required for their sustainable uses.
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HIV-1 infection is considered one of the major public health problems worldwide. Due to the limited access to antiretroviral therapy, the associated side effects, and the resistance that the virus can generate, it has become necessary to continue the development of new antiviral agents. The study aimed to identify potential antiviral agents for HIV-1 by evaluating the in vitro and in silico activity of 16 synthetic di-halogenated compounds derived from L-Tyrosine. The compounds were tested for cytotoxicity, which was determined using MTT, and a combined antiviral screening strategy (pre- and post-infection treatment) was performed against R5 and X4 strains of HIV-1. The most promising compounds were evaluated against a pseudotyped virus (HIV-GFP-VSV-G), and the effectiveness of these compounds was measured through GFP flow cytometry. Also, the antiviral effect of these compounds was evaluated in PBMCs using flow cytometry and ELISA for p24. The TODB-2M, TODC-2M, TODC-3M, and YDC-3M compounds showed low toxicity and significant inhibitory activity against HIV-1. In silico docking and molecular dynamics assays suggest that the compounds' antiviral activity may be due to interaction with reverse transcriptase, viral protease, or envelope gp120.
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How the human body reacts to the exposure of HIV-1 is an important research goal. Frequently, HIV exposure leads to infection, but some individuals show natural resistance to this infection; they are known as HIV-1-exposed but seronegative (HESN). Others, although infected but without antiretroviral therapy, control HIV-1 replication and progression to AIDS; they are named controllers, maintaining low viral levels and an adequate count of CD4+ T lymphocytes. Biological mechanisms explaining these phenomena are not precise. In this context, metabolomics emerges as a method to find metabolites in response to pathophysiological stimuli, which can help to establish mechanisms of natural resistance to HIV-1 infection and its progression. We conducted a cross-sectional study including 30 HESN, 14 HIV-1 progressors, 14 controllers and 30 healthy controls. Plasma samples (directly and deproteinized) were analyzed through Nuclear Magnetic Resonance (NMR) metabolomics to find biomarkers and altered metabolic pathways. The metabolic profile analysis of progressors, controllers and HESN demonstrated significant differences with healthy controls when a discriminant analysis (PLS-DA) was applied. In the discriminant models, 13 metabolites associated with HESN, 14 with progressors and 12 with controllers were identified, which presented statistically significant mean differences with healthy controls. In progressors, the metabolites were related to high energy expenditure (creatinine), mood disorders (tyrosine) and immune activation (lipoproteins), phenomena typical of the natural course of the infection. In controllers, they were related to an inflammation-modulating profile (glutamate and pyruvate) and a better adaptive immune system response (acetate) associated with resistance to progression. In the HESN group, with anti-inflammatory (lactate and phosphocholine) and virucidal (lactate) effects which constitute a protective profile in the sexual transmission of HIV. Concerning the significant metabolites of each group, we identified 24 genes involved in HIV-1 replication or virus proteins that were all altered in progressors but only partially in controllers and HESN. In summary, our results indicate that exposure to HIV-1 in HESN, as well as infection in progressors and controllers, affects the metabolism of individuals and that this affectation can be determined using NMR metabolomics.
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The aim of this study was to evaluate the levels of chemical markers in raw cacao beans in two clones (introduced and regional) in Colombia over several years. Multivariate statistical methods were used to analyze the flavanol monomers (epicatechin and catechin), flavanol oligomers (procyanidins) and methylxanthine alkaloids (caffeine and theobromine) of cocoa samples. The results identified genotype as the main factor contributing to cacao chemistry, although significant differences were not observed between universal and regional clones in PCA. The univariate analysis allowed us to establish that EET-96 had the highest contents of both flavanol monomers (13.12 ± 2.30 mg/g) and procyanidins (7.56 ± 4.59 mg/g). In addition, the geographic origin, the harvest conditions of each region and the year of harvest may contribute to major discrepancies between results. Turbo cocoa samples are notable for their higher flavanol monomer content, Chigorodó cocoa samples for the presence of both types of polyphenol (monomer and procyanidin contents) and the Northeast cocoa samples for the higher methylxanthine content. We hope that knowledge of the heterogeneity of the metabolites of interest in each clone will contribute to the generation of added value in the cocoa production chain and its sustainability.
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Cacao , Catequina , Proantocianidinas , Cacao/química , Catequina/química , Colombia , Productos Agrícolas , Flavonoides/análisis , Genotipo , Polifenoles/análisis , Proantocianidinas/análisis , XantinasRESUMEN
Background: Coronavirus infectious disease 2019 (COVID-19) caused by the infection with the new coronavirus SARS-CoV-2 has affected the life and health of more than 222 million people. In the absence of any specific pharmacological treatment, the need to find new therapeutic alternatives is clear. Medicinal plants are widely used worldwide to treat different conditions, including COVID-19; however, in most cases, there are no specific studies to evaluate the efficacy of these treatments. Objective: This article evaluates the antiviral effect of six plant extracts used by indigenous and afro Colombian people against SARS-CoV-2 in vitro. Methods: The antiviral effect of six extracts prepared from plants used in Colombian traditional medicine was evaluated against SARS-CoV-2 through a pre-post treatment strategy on the Vero E6 cell line. Once cytotoxicity was established through an MTT assay, the antiviral effect of the extracts was calculated based on the reduction in the viral titer determined by plaque assay. Results:Gliricidia sepium inhibited SARS-CoV-2 in a 75.6%, 56.8%, 62.5% and 40.0% at 10 mg/mL, 8 mg/mL, 6 mg/mL, and 2 mg/mL, respectively, while Piper tuberculatumtreatment reduced viral titer in 33.3% at 6 mg/mL after 48h. Conclusion:G. sepium and P. tuberculatum extracts exhibit antiviral activity against SARS-CoV-2 in vitro
Introducción: La enfermedad infecciosa causada por el coronavirus 2019 (COVID-19) generada por la infección con el nuevo coronavirus SARS-CoV-2 ha afectado la vida y la salud de mas de 222 millones de personas. En ausencia de algún tratamiento farmacológico específico, la necesidad de encontrar nuevas alternativas terapéuticas es clara. Las plantas medicinales son utilizadas en todo el mundo para tratar diferentes condiciones, incluyendo el COVID-19; sin embargo, en la mayoría de los casos no existen estudios específicos que evalúen la eficacia de estos tratamientos. Objetivo: En este artículo, evaluamos el efecto antiviral de seis extractos de plantas usadas por pueblos indígenas y afrocolombianos contra el SARS-CoV-2 in vitro.Metodología: El efecto antiviral de seis extractos preparados a partir de plantas usadas en medicina tradicional colombiana fue evaluado contra SARS-CoV-2 por medio de una estrategia de pre-post tratamiento en células Vero E6. Una vez se estableció la citotoxicidad por un ensayo de MTT, el efecto antiviral de estos extractos fue calculado basado en la reducción del título viral determinado por ensayo de plaqueo. Resultados:G. sepium inhibió SARS-CoV-2 en un 75.6%, 56.8%, 62.5% y 40.0% a 10 mg/mL, 8 mg/mL, 6 mg/mL, and 2 mg/mL, respectivamente. Mientras el extracto de Piper tuberculatum redujo el título viral en un 33.3% a 6 mg/mL luego de 48h de tratamiento
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Antivirales/farmacología , Plantas Medicinales/química , Extractos Vegetales/farmacología , SARS-CoV-2/efectos de los fármacos , ColombiaRESUMEN
Infections caused by human immunodeficiency virus (HIV) are considered one of the main public health problems worldwide. Antiretroviral therapy (ART) is the current modality of treatment for HIV-1 infection. It comprises the combined use of several drugs and can decrease the viral load and increase the CD4+ T cell count in patients with HIV-1 infection, thereby proving to be an effective modality. This therapy significantly decreases the rate of morbidity and mortality owing to acquired immunodeficiency syndrome (AIDS) and prolongs and improves the quality of life of infected patients. However, nonadherence to ART may increase viral resistance to antiretroviral drugs and transmission of drug-resistant strains of HIV. Therefore, it is necessary to continue research for compounds with anti-HIV-1 activity, exhibiting a potential for the development of an alternative or complementary therapy to ART with low cost and fewer side effects. Natural products and their derivatives represent an excellent option owing to their therapeutic potential against HIV. Currently, the derivatives of natural products available as anti-HIV-1 agents include zidovudine, an arabinonucleoside derivative of the Caribbean marine sponge (Tectitethya crypta), which inhibits the reverse transcriptase of the virus. This was the first antiviral agent approved for treatment of HIV infection. Additionally, bevirimat (isolated from Syzygium claviflorum) and calanolide A (isolated from Calophyllum sp.) are inhibitors of viral maturation and reverse transcription process, respectively. In the present review, we aimed to describe the wide repertoire of natural compounds exhibiting anti-HIV-1 activity that can be considered for designing new therapeutic strategies to curb the HIV pandemic.
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Despite the serious public health problem represented by the diseases caused by dengue (DENV), Zika (ZIKV) and chikungunya (CHIKV) viruses, there are still no specific licensed antivirals available for their treatment. Here, we examined the potential anti-arbovirus activity of ten di-halogenated compounds derived from L-tyrosine with modifications in amine and carboxyl groups. The activity of compounds on VERO cell line infection and the possible mechanism of action of the most promising compounds were evaluated. Finally, molecular docking between the compounds and viral and cellular proteins was evaluated in silico with Autodock Vina®, and the molecular dynamic with Gromacs®. Only two compounds (TDC-2M-ME and TDB-2M-ME) inhibited both ZIKV and CHIKV. Within the possible mechanism, in CHIKV, the two compounds decreased the number of genome copies and in the pre-treatment strategy the infectious viral particles. In the ZIKV model, only TDB-2M-ME inhibited the viral protein and demonstrate a virucidal effect. Moreover, in the U937 cell line infected with CHIKV, both compounds inhibited the viral protein and TDB-2M-ME inhibited the viral genome too. Finally, the in silico results showed a favorable binding energy between the compounds and the helicases of both viral models, the NSP3 of CHIKV and cellular proteins DDC and ß2 adrenoreceptor.
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Antivirales/síntesis química , Virus Chikungunya/efectos de los fármacos , Virus del Dengue/efectos de los fármacos , Fenoles/síntesis química , Tirosina/análogos & derivados , Virus Zika/efectos de los fármacos , Animales , Antivirales/química , Antivirales/farmacología , Línea Celular , Virus Chikungunya/genética , Virus Chikungunya/metabolismo , Chlorocebus aethiops , Virus del Dengue/genética , Genoma Viral/efectos de los fármacos , Halogenación , Humanos , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Estructura Molecular , Fenoles/química , Fenoles/farmacología , Células Vero , Virus Zika/genética , Virus Zika/metabolismoRESUMEN
Leishmania parasites cause leishmaniasis, one of the most epidemiologically important neglected tropical diseases. Leishmania exhibits a high ability of developing drug resistance, and drug resistance is one of the main threats to public health, as it is associated with increased incidence, mortality, and healthcare costs. The antimonial drug is the main historically implemented drug for leishmaniasis. Nevertheless, even though antimony resistance has been widely documented, the mechanisms involved are not completely understood. In this study, we aimed to identify potential metabolite biomarkers of antimony resistance that could improve leishmaniasis treatment. Here, using L. tropica promastigotes as the biological model, we showed that the level of response to antimony can be potentially predicted using 1H-NMR-based metabolomic profiling. Antimony-resistant parasites exhibited differences in metabolite composition at the intracellular and extracellular levels, suggesting that a metabolic remodeling is required to combat the drug. Simple and time-saving exometabolomic analysis can be efficiently used for the differentiation of sensitive and resistant parasites. Our findings suggest that changes in metabolite composition are associated with an optimized response to the osmotic/oxidative stress and a rearrangement of carbon-energy metabolism. The activation of energy metabolism can be linked to the high energy requirement during the antioxidant stress response. We also found that metabolites such as proline and lactate change linearly with the level of resistance to antimony, showing a close relationship with the parasite's efficiency of drug resistance. A list of potential metabolite biomarkers is described and discussed.
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Antimonio/toxicidad , Antiprotozoarios/toxicidad , Resistencia a Medicamentos , Leishmania tropica/metabolismo , Metaboloma , Metabolismo Energético , Leishmania tropica/efectos de los fármacos , Presión Osmótica , Estrés OxidativoRESUMEN
Promising research over the past decades has shown that some types of pentacyclic triterpenes (PTs) are associated with the prevention of type 2 diabetes (T2D), especially those found in foods. The most abundant edible sources of PTs are those belonging to the ursane and oleanane scaffold. The principal finding is that Cecropia telenitida contains abundant oleanane and ursane PT types with similar oxygenation patterns to those found in food matrices. We studied the compositional profile of a rich PT fraction (DE16-R) and carried out a viability test over different cell lines. The biosynthetic pathway connected to the isolated PTs in C. telenitida offers a specific medicinal benefit related to the modulation of T2D. This current study suggests that this plant can assemble isobaric, positional isomers or epimeric PT. Ursane or oleanane scaffolds with the same oxygenation pattern are always shared by the PTs in C. telenitida, as demonstrated by its biosynthetic pathway. Local communities have long used this plant in traditional medicine, and humans have consumed ursane and oleanane PTs in fruits since ancient times, two key points we believe useful in considering the medicinal benefits of C. telenitida and explaining how a group of molecules sharing a closely related scaffold can express effectiveness.
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Vías Biosintéticas , Cecropia/química , Suplementos Dietéticos , Triterpenos Pentacíclicos/metabolismo , Animales , Muerte Celular/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Fraccionamiento Químico , Cromatografía Líquida de Alta Presión , Humanos , Espectroscopía de Resonancia Magnética , Ratones , Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/farmacologíaRESUMEN
Human peripheral blood mononuclear cells (PBMCs) are part of the innate and adaptive immune system, and form a critical interface between both systems. Studying the metabolic profile of PBMC could provide valuable information about the response to pathogens, toxins or cancer, the detection of drug toxicity, in drug discovery and cell replacement therapy. The primary purpose of this study was to develop an improved processing method for PBMCs metabolomic profiling with nuclear magnetic resonance (NMR) spectroscopy. To this end, an experimental design was applied to develop an alternative method to process PBMCs at low concentrations. The design included the isolation of PBMCs from the whole blood of four different volunteers, of whom 27 cell samples were processed by two different techniques for quenching and extraction of metabolites: a traditional one using organic solvents and an alternative one employing a high-intensity ultrasound probe, the latter with a variation that includes the use of deproteinizing filters. Finally, all the samples were characterized by 1H-NMR and the metabolomic profiles were compared by the method. As a result, two new methods for PBMCs processing, called Ultrasound Method (UM) and Ultrasound and Ultrafiltration Method (UUM), are described and compared to the Folch Method (FM), which is the standard protocol for extracting metabolites from cell samples. We found that UM and UUM were superior to FM in terms of sensitivity, processing time, spectrum quality, amount of identifiable, quantifiable metabolites and reproducibility.
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Leucocitos Mononucleares/metabolismo , Espectroscopía de Resonancia Magnética , Metabolómica , Manejo de Especímenes/métodos , Adulto , Humanos , Leucocitos Mononucleares/citología , Masculino , Persona de Mediana EdadRESUMEN
The commercial copolymers Eudragit® E 100 and Eudragit® PO are widely used materials in the pharmaceutical field as coating systems. Such materials derived from amino-methacrylate groups under acidulated conditions may acquire an ionisable fraction or undergo hydrolytic degradation of the polymeric structure. This work focused on establishing the chemical, physical, and surface changes of two reprocessed polymeric materials, here named as EuCl-E-100 and EuCl-E-PO, which were obtained from the commercial Eudragit® E 100 and Eudragit® E PO, respectively. The commercial materials were exposed to extreme acid conditions, where the polymers were solubilised and subsequently dried by the refractance window method. The materials obtained were chemically characterised by potentiometric titration, nuclear magnetic resonance spectroscopy (1H NMR and 13C NMR) in one and two dimensions (COSY, HSQC, and HMBC), infrared spectroscopy, X-ray diffraction, and differential scanning calorimetry. Changes in the physical properties of the materials were evaluated through studies of flowability, compactability, and their ability to gain and lose humidity. Surface thermodynamic studies were carried out through contact angle measurements using the sessile drop method. The results showed that the processed polymeric materials acquired a substantial degree of ionisation without undergoing hydrolysis of the esterified groups. Furthermore, such changes improved the flow characteristics of the material and the solubility in aqueous media at pH > 5, while also maintaining the hydrophobicity degree of the polymeric surface.
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Background: Human immunodeficiency virus type 1 (HIV-1) infection and Acquired immunodeficiency syndrome are mayor global public health issues. HIV-1 infection is now manageable as a chronic disease thanks to the development of antiretroviral therapy; however, the existence of HIV drug resistance and collateral effects have increased the search for therapeutic alternatives. Compounds of marine resources have been studied for their antiviral potential. Objectives: To evaluate the antiviral activity of isolated bromotyrosine-derivative compounds from the Colombian marine sponges, Verongula rigida and Aiolochoria crassa against HIV-1 infection in vitro. Methods: Cytotoxicity of 11 bromotyrosine-derivative compounds was determined by the MTT assay. Inhibition of HIV-1 replication was performed using the U373-MAGI cell line, which was infected with recombinant green fluorescent protein (GFP)-expressing viruses pseudotyped, in the presence or absence of the compounds. The percentage of infected cells was evaluated by flow cytometry. In addition, the inhibition of reverse transcription and nuclear import was determined by quantification of early and late reverse transcription products and 2-LTR circles, respectively, using quantitative PCR. Results: Aeroplysinin-1, purealidin B and 3-bromo-5-hydroxy-Omethyltyrosine inhibited the HIV-1 replication in a dose-dependent manner, with a median maximum percentage of inhibition of 74% (20 µM), 57% (80 µM) and 47% (80 µM), respectively. Importantly, none of these concentrations were cytotoxic. Aeroplysinin-1, 19-deoxyfistularin 3, purealidin B, fistularin 3 and 3-bromo-5-hydroxy-O-methyltyrosine inhibited the nuclear import efficiently; while 3,5-dibromoN,N,N,O-tetramethyltyraminium, aeroplysinin-1, purealidin B, fistularin 3 and 3-bromo-5-hydroxy-Omethyltyrosine inhibited X4 HIV-1 cell entry with a median maximum percentage of inhibition ranging between 2 to 30%. Conclusions: Aeroplysinin-1, 19-deoxyfistularin 3, purealidin B, fistularin 3 and 3-bromo-5-hydroxy-O-methyltyrosine inhibited HIV replication at different steps. This study opens the possibility of chemically synthesizing these compounds and evaluating them as alternative therapies against HIV-1.
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Humanos , VIH , Poríferos , Recursos Marinos , Síndromes de InmunodeficienciaRESUMEN
Nine bromotyrosine-derived compounds were isolated from the Caribbean marine sponge Verongula rigida. Two of them, aeroplysinin-1 (1) and dihydroxyaerothionin (2), are known compounds for this species, and the other seven are unknown compounds for this species, namely: 3,5-dibromo-N,N,N-trimethyltyraminium (3), 3,5-dibromo-N,N,N, O-tetramethyltyraminium (4), purealidin R (5), 19-deoxyfistularin 3 (6), purealidin B (7), 11-hydroxyaerothionin (8) and fistularin-3 (9). Structural determination of the isolated compounds was performed using one- and two-dimensional NMR, MS and other spectroscopy data. All isolated compounds were screened for their in vitro activity against three parasitic protozoa: Leishmania panamensis, Plasmodium falciparum and Trypanosoma cruzi. Compounds 7 and 8 showed selective antiparasitic activity at 10 and 5 µM against Leishmania and Plasmodium parasites, respectively. Cytotoxicity of these compounds on a human promonocytic cell line was also assessed.
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Antiparasitarios/farmacología , Poríferos/química , Tirosina/análogos & derivados , Animales , Antimaláricos/química , Antimaláricos/aislamiento & purificación , Antimaláricos/farmacología , Antiparasitarios/química , Antiparasitarios/aislamiento & purificación , Antiprotozoarios/química , Antiprotozoarios/aislamiento & purificación , Antiprotozoarios/farmacología , Leishmania/efectos de los fármacos , Plasmodium falciparum/efectos de los fármacos , Tripanocidas/química , Tripanocidas/aislamiento & purificación , Tripanocidas/farmacología , Trypanosoma cruzi/efectos de los fármacos , Tirosina/química , Tirosina/aislamiento & purificación , Tirosina/farmacologíaRESUMEN
Marine organisms represent a new extensive source for bioactive molecules. They have the potential to provide new therapeutic alternatives to treat human diseases. In this paper, we describe and discuss a variety of isolated and semisynthetic molecules obtained from marine sources. These compounds are in phase II, phase III and at the commercialization stage of new drug development. A description of the mechanism of action, dosage used and side effects are also reported. The positive results obtained from these studies have triggered the development of new studies to evaluate the prospects for utilization of marine organisms.
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Productos Biológicos/farmacología , Descubrimiento de Drogas , Animales , Productos Biológicos/aislamiento & purificación , Océanos y MaresRESUMEN
La bioautografía es una técnica sencilla y rápida que combina las ventajas de la cromatografía en capa fina y la detección de actividad antimicrobiana, logrando visualizar directamente la(s) fracción(es) con actividad antimicrobiana. Determinar la eficacia de esta técnica puede facilitar el panorama en el aislamiento de sustancias antimicrobianas presentes en mezclas complejas. El trabajo descrito es un avance para evaluar si la técnica permite cuantificar la actividad antimicrobiana empleando como referencia el aminoglicósido Gentamicina®y su actividad contra el microorganismo patógeno Escherichia coli (E.coli). La cuantificación de la actividad antimicrobiana se verifica al medir el diámetro del halo de difusión que se genera al aplicar soluciones de diferentes concentraciones de Gentamicina sobre placas cromatográficas; al determinar luego el efecto del volumen aplicado sobre la variabilidad de los resultados y finalmente al analizar las diferencias entre los halosde difusión y de inhibición microbiana. En el presente estudio se encuentra que la difusión del antibióticosobre las placas es un factor determinante para cuantificar, y que existe un rango de concentraciones donde la fuerte interacción entre las variables aludidas permite predecir que se cuenta con un método validable para detectar y cuantificar la actividad antimicrobiana, sobre todo en mezclas complejas.
Asunto(s)
Escherichia coli , GentamicinasRESUMEN
Se presentan los valores obtenidos, en el proceso de evaluación y desarrollo de métodos, para el control de calidad de 11 de las plantas medicinales aprobadas en Colombia: Semillas de anís (Pimpinella anisum), bulbos de ajo (Allium sativum), corteza de canela (Cinnamomum zeylanicum.), semillas de cardamomo (Elettaria cardamomum), flores de caléndula (Calendula officinalis), raíces de genciana (Gentiana lutea), hojas de hamamelis (Hammamelis virginiana), semillas de lino (Linum usitatissimum), semillas entera de trigo (Triticum aestivum), rizomas y raíces de valeriana (Valeriana officinalis) y flores de manzanilla (Matricaria chamomilla). Los análisis realizados a cada planta medicinal comprenden: La descripción morfológica macro- y microscópica, la cuantificación de cenizas totales, el contenido de sustancias extraíbles, la pérdida de peso por secado, el contenido de aceites esenciales y la identificación por cromatografía de capa fina de marcadores taxonómicos
Asunto(s)
Plantas Medicinales , Control de Calidad , Valores de ReferenciaRESUMEN
En este artículo se presenta una revisión que comprende una selección de 60 artículos en los que se reportan los estudios de actividad antibacteriana, antimicótica y antiviral de compuestos derivados de plantas, organismos marinos, microorganismos y otras fuentes naturales, en el período comprendido entre 1976 y 2003. Se reportan 159 especies de plantas y 39 especies de microorganismos. Esta recopilación es útil para investigadores en el área de la química y la actividad biológica de los productos naturales bioactivos.