RESUMO
Interest in antiviral plant species has grown exponentially and some have been reported to have anti-HIV properties. This research aims to perform the bio-guided phytochemical fractionation by antiretroviral activity of Lafoensia pacari stem barks. This in vitro experimental study involved the preparation of plant material, obtention of ethanolic extract, fractionation, purification, identification and quantification of fractions, acid-base extraction, nuclear magnetic resonance, HIV-1 RT inhibition test and molecular docking studies. From the bio-guided fractionation by the antiretroviral activity there was a higher activity in the acetanolic subfractions, highlighting the acetate subfraction - neutrals with 60.98% of RT inhibition and ellagic acid with 88.61% of RT inhibition and absence of cytotoxicity. The macrophage lineage cytotoxicity assay showed that the chloroform fraction was more toxic than the acetate fraction. The analysis of the J-resolved spectrum in the aromatic region showed a singlet at 7.48 and 6.93 ppm which was identified as ellagic acid and gallic acid, respectively. The 5TIQ enzyme obtained better affinity parameter with the ellagic acid ligand, which was confirmed by the HSQC-1H-13C spectra. Gallic acid was also favorable to form interaction with the 5TIQ enzyme, being confirmed through the HSQC-1H-13C spectrum. From the PreADMET evaluation it was found that ellagic acid is a promising molecule for its RT inhibition activity and pharmacokinetic and toxicity parameters.
Assuntos
Infecções por HIV , Lythraceae , Acetatos , Ácido Elágico/farmacologia , Ácido Gálico/farmacologia , Lythraceae/química , Simulação de Acoplamento Molecular , Extratos Vegetais/toxicidadeRESUMO
Interest in antiviral plant species has grown exponentially and some have been reported to have anti-HIV properties. This research aims to perform the bio-guided phytochemical fractionation by antiretroviral activity of Lafoensia pacari stem barks. This in vitro experimental study involved the preparation of plant material, obtention of ethanolic extract, fractionation, purification, identification and quantification of fractions, acid-base extraction, nuclear magnetic resonance, HIV-1 RT inhibition test and molecular docking studies. From the bio-guided fractionation by the antiretroviral activity there was a higher activity in the acetanolic subfractions, highlighting the acetate subfraction - neutrals with 60.98% of RT inhibition and ellagic acid with 88.61% of RT inhibition and absence of cytotoxicity. The macrophage lineage cytotoxicity assay showed that the chloroform fraction was more toxic than the acetate fraction. The analysis of the J-resolved spectrum in the aromatic region showed a singlet at 7.48 and 6.93 ppm which was identified as ellagic acid and gallic acid, respectively. The 5TIQ enzyme obtained better affinity parameter with the ellagic acid ligand, which was confirmed by the HSQC-1H-13C spectra. Gallic acid was also favorable to form interaction with the 5TIQ enzyme, being confirmed through the HSQC-1H-13C spectrum. From the PreADMET evaluation it was found that ellagic acid is a promising molecule for its RT inhibition activity and pharmacokinetic and toxicity parameters.
O interesse por espécies vegetais com ação antiviral tem crescido exponencialmente e algumas tem sido relatadas como possuídoras de propriedades anti-HIV. Essa pesquisa tem como objetivo realizar o fracionamento fitoquímico biodirecionado pela atividade antirretroviral das cascas do caule da espécie Lafoensia pacari. Trata-se de um estudo experimental in vitro e a metodologia envolve preparo do material vegetal, obtenção do extrato etanólico, fracionamento, purificação, identificação e quantificação das frações, extração ácido-base, ressonância magnética nuclear, teste de inibição da TR do HIV-1 e estudos de docking molecular. A partir do fracionamento biodirecionado pela atividade antirretroviral verificou-se uma maior atividade nas subfrações acetanólica. Com destaque para a subfração acetanólica neutros com 60,98% de inibição de TR e o ácido elágico com 88,61% de inibição de TR e ausência de citotoxicidade. Verificou-se com o teste de citotoxicidade em linhagem de macrófagos que a fração clorofórmica foi mais tóxica que a fração acetanólica. A análise do espectro J-resolvido na região aromática apresentou um simpleto em 7.48 e 6.93 ppm que foram identificados como ácido elágico e ácido gálico respectivamente. A enzima 5TIQ obteve melhor parâmetro de afinidade com o ligante ácido elágico que foi confirmado pelos espectros HSQC-1H-13C. O ácido gálico mostrou-se também favorável a formar interação com a enzima 5TIQ, sendo confirmado através do espectro HSQC-1H-13C. Através da avaliação do PreADMET verificou-se que o ácido elágico é uma molécula promissora pela sua atividade de inibição da TR e parâmetros farmacocinéticos e de toxicidade.
Assuntos
HIV , Antirretrovirais , Simulação de Acoplamento Molecular , Macrófagos , FitoterapiaRESUMO
Between the April and July of 2007, patients undergoing treatment for schistosomal liver fibrosis, at a university hospital in north-eastern Brazil, were examined by transthoracic Doppler echocardiography (TTE). The main aim was to determine the prevalence of pulmonary hypertension in the patients. The thorax of each patient who had such hypertension, as indicated by an estimated pulmonary arterial systolic pressure (PASP) in excess of 35 mmHg, was then investigated by contrast-enhanced multidetector-row computed tomography (MDCT). The 84 patients (53 women and 31 men) enrolled in the study had a mean (S.D.) age of 50.06 (12.25) years. Nine (10.7%, with a 95% confidence interval of 5.0%-19.4%) of the patients were found to have pulmonary hypertension, with PASP ranging from 40-126 mmHg, and a median (S.D.) PASP of 58.78 (28.01) mmHg. The contrast-enhanced thoracic MDCT indicated that most of the patients with pulmonary hypertension had a pulmonary artery trunk that was unusually wide (67%) and more than 1.1-fold wider than the ascending aorta (56%), dilatation of the main pulmonary arteries (100%), a segmental artery that, in diameter, was more than 1.1-fold larger than the adjacent bronchi (89%), tapering of the peripheral pulmonary arteries (78%), and cardiac enlargement (78%). No patient suffered pulmonary embolism as a result of the investigations. The prevalence of pulmonary hypertension in the patients with schistosomal liver fibrosis (10.7%) justifies the screening of such patients by TTE.