Molecular docking studies and evaluation of the antiretroviral activity and cytotoxicity of the species Lafoensia pacari Saint-Hilaire

Abstract 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. Resumo 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 citotoxicidad