title: Anti-HIV-1 integrase effect of compounds from Aglaia andamanica leaves and molecular docking study with acute toxicity test in mice.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: a Department of Pharmacognosy and Pharmaceutical Botany , Faculty of Pharmaceutical Sciences, Prince of Songkla University , Hat-Yai, Songkhla , Thailand .
authors.forename: Jindaporn
authors.initials: J
authors.lastname: Puripattanavong
authors.affiliation: a Department of Pharmacognosy and Pharmaceutical Botany , Faculty of Pharmaceutical Sciences, Prince of Songkla University , Hat-Yai, Songkhla , Thailand .
authors.forename: Pattreeya
authors.initials: P
authors.lastname: Tungcharoen
authors.affiliation: a Department of Pharmacognosy and Pharmaceutical Botany , Faculty of Pharmaceutical Sciences, Prince of Songkla University , Hat-Yai, Songkhla , Thailand .|b Excellent Research Laboratory, Phytomedicine and Pharmaceutical Biotechnology Excellence Center, Faculty of Pharmaceutical Sciences, Prince of Songkla Univesity , Songkhla , Thailand , and.
authors.forename: Prapaporn
authors.initials: P
authors.lastname: Chaniad
authors.affiliation: c Department of Chemistry , Faculty of Science, Chulalongkorn University , Pathumwan , Bangkok , Thailand.
authors.forename: Somsak
authors.initials: S
authors.lastname: Pianwanit
authors.affiliation: a Department of Pharmacognosy and Pharmaceutical Botany , Faculty of Pharmaceutical Sciences, Prince of Songkla University , Hat-Yai, Songkhla , Thailand .|b Excellent Research Laboratory, Phytomedicine and Pharmaceutical Biotechnology Excellence Center, Faculty of Pharmaceutical Sciences, Prince of Songkla Univesity , Songkhla , Thailand , and.
authors.forename: Supinya
authors.initials: S
authors.lastname: Tewtrakul
mesh_terms: D031602:Aglaia; D000818:Animals; D005260:Female; D019427:HIV Integrase / Q000378:metabolism; D019428:HIV Integrase Inhibitors / Q000302:isolation & purification / Q000378:metabolism* / Q000633:toxicity; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051379:Mice; D062105:Molecular Docking Simulation / Q000379:methods*; D010936:Plant Extracts / Q000302:isolation & purification / Q000378:metabolism* / Q000633:toxicity; D018515:Plant Leaves; D023382:Toxicity Tests, Acute / Q000379:methods*
chemical_list: D019428:HIV Integrase Inhibitors; D010936:Plant Extracts; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1
keywords: Meliaceae; multiplate integration assay; proline derivative; up and down method