title: Anti-HIV-1 integrase compounds from Dioscorea bulbifera and molecular docking study.
abstract: BACKGROUND
  Dioscorea bulbifera L. (Dioscoreaceae) has been used in a traditional Thai longevity medicine preparation. Isolation of inhibitors from natural products is a potential source for continuous development of new HIV-1 integrase (IN) inhibitors.
  
  
  OBJECTIVE
  The objective of this study is to isolate the compounds and evaluate their anti-HIV-1 IN activity, as well as to predict the potential interactions of the compounds with an IN.
  
  
  METHODS
  The ethyl acetate and water fractions (1-100 μg/mL) of Dioscorea bulbifera bulbils were isolated and tested for their anti-HIV-1 IN activity using the multiplate integration assay (MIA). The interactions of the active compounds with IN were investigated using a molecular docking method.
  
  
  CONCLUSIONS
  The ethyl acetate and water fractions of Dioscorea bulbifera bulbils afforded seven compounds. Among these, allantoin (1), 2,4,3',5'-tetrahydroxybibenzyl (2), and 5,7,4'-trihydroxy-2-styrylchromone (5) were isolated for the first time from this plant. Myricetin (4) exhibited the most potent activity with an IC50 value of 3.15 μM, followed by 2,4,6,7-tetrahydroxy-9,10-dihydrophenanthrene (3, IC50 value= 14.20 μM), quercetin-3-O-β-D-glucopyranoside (6, IC50 value = 19.39 μM) and quercetin-3-O-β-D-galactopyranoside (7, IC50 value = 21.80 μM). Potential interactions of the active compounds (3, 4, 6, and 7) with the IN active site were additionally investigated. Compound 4 showed the best binding affinity to IN and formed strong interactions with various amino acid residues. These compounds interacted with Asp64, Thr66, His67, Glu92, Asp116, Gln148, Glu152, Asn155, and Lys159, which are involved in both the 3'-processing and strand transfer reactions of IN. In particular, galloyl, catechol, and sugar moieties were successful inhibitors for HIV-1 IN.
authors: a Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences , Prince of Songkla University , Songkhla , Thailand ;
authors: Prapaporn
authors: P
authors: Chaniad
authors: a Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences , Prince of Songkla University , Songkhla , Thailand ;|b Excellent Research Laboratory, Phytomedicine and Pharmaceutical Biotechnology Excellent Center, Faculty of Pharmaceutical Sciences , Prince of Songkla University , Songkhla , Thailand ;
authors: Chatchai
authors: C
authors: Wattanapiromsakul
authors: c Department of Chemistry, Faculty of Science , Chulalongkorn University , Bangkok , Pathumwan , Thailand.
authors: Somsak
authors: S
authors: Pianwanit
authors: a Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences , Prince of Songkla University , Songkhla , Thailand ;|b Excellent Research Laboratory, Phytomedicine and Pharmaceutical Biotechnology Excellent Center, Faculty of Pharmaceutical Sciences , Prince of Songkla University , Songkhla , Thailand ;
authors: Supinya
authors: S
authors: Tewtrakul
mesh_terms: D027742:Dioscorea / Q000737:chemistry*; D019427:HIV Integrase / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D020128:Inhibitory Concentration 50; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D019428:HIV Integrase Inhibitors; D010936:Plant Extracts; D019427:HIV Integrase
keywords: 2,4,3′,5′-tetrahydroxybibenzyl; 5,7,4′-trihydroxyl-2-styrylchromone; Allantoin; Dioscoreaceae; integrase