Anti-HIV-1 integrase effect of compounds from Aglaia andamanica leaves and molecular docking study with acute toxicity test in mice

摘要

Abstract Context: Acquired immunodeficiency syndrome (AIDS) is a serious health problem worldwide. It has been reported that Aglaia andamanica Hiern (Meliaceae) leaves possessed an antiviral effect. Therefore, a search of anti-HIV-1 integrase (HIV-1 IN) agents from A. andamanica is a promising target. Objective: The objective of this study is to evaluate anti-HIV-1 IN activity of isolated compounds from A. andamanica using an in vitro assay and molecular docking study as well as testing acute toxicity in mice using the up and down method. Materials and methods: The leaves and compounds (3–100?μg/mL) from A. andamanica were determined for the anti-HIV-1 IN effect using the multiplate integration assay (MIA) by detection the absorbance of the final product, p-nitrophenol, at 405?nm. The molecular docking with the HIV-1 IN of the active compound N-methyl-trans-4-hydroxy- l -proline ( 10 ) was also studied. The Swiss albino mice were used for an acute toxicity test. Results and discussion: Among the isolated compounds, 10 showed marked anti-HIV-1 IN effect with an IC₅₀ value of 11.8?μg/mL, whereas other compounds were inactive (IC₅₀ value?>?100?μg/mL). The molecular docking of compound 10 with an HIV-1 IN enzyme was also studied. The result revealed that this compound formed the hydrogen bonding with the Thr66, Asn155, and Lys159 of the HIV-1 IN binding site. The acute toxicity of the A. andamanica extract was not observed at the dose 2000?mg/kg mice. This is the first report of A. andamanica for anti-HIV-1 IN activity.