A docking study of l-chicoric acid with HIV-1 integrase

Healy, Eamonn F.; Sanders, Jonathan; King, Peter; Robinson, William E.

doi:10.1016/j.jmgm.2008.09.011

Cited by 37 publications

(37 citation statements)

References 27 publications

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“…For each compound, all 100 independent conformations were clustered into groups with a criterion of the root mean-square deviation (RMSD) of less than 2 Å. The best-docked conformation was selected from a cluster with the lowest binding energy and containing the greatest number of conformations (Healy et al 2009). The amino acid residues within 6 Å of the ligand in the IN active site were chosen for the analysis of hydrogen bond interaction.…”

Section: Dockingmentioning

confidence: 99%

Anti-HIV-1 integrase compounds from Dioscorea bulbifera and molecular docking study

Chaniad

Wattanapiromsakul

Pianwanit

et al. 2016

Pharmaceutical Biology

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Context 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. Materials and methods The ethyl acetate and water fractions (1-100 mg/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. Results and discussions The ethyl acetate and water fractions of Dioscorea bulbifera bulbils afforded seven compounds. Among these, allantoin (1), 2,4,3 0 ,5 0 -tetrahydroxybibenzyl (2), and 5,7,4 0 -trihydroxy-2-styrylchromone (5) were isolated for the first time from this plant. Myricetin (4) exhibited the most potent activity with an IC 50 value of 3.15 mM, followed by 2,4,6,7-tetrahydroxy-9,10-dihydrophenanthrene (3, IC 50 value¼ 14.20 mM), quercetin-3-O-b-D-glucopyranoside (6, IC 50 value ¼ 19.39 mM) and quercetin-3-O-b-D-galactopyranoside (7, IC 50 value ¼ 21.80 mM). 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 0 -processing and strand transfer reactions of IN. In particular, galloyl, catechol, and sugar moieties were successful inhibitors for HIV-1 IN.ARTICLE HISTORY

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Section: Dockingmentioning

confidence: 99%

Anti-HIV-1 integrase compounds from Dioscorea bulbifera and molecular docking study

Chaniad

Wattanapiromsakul

Pianwanit

et al. 2016

Pharmaceutical Biology

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“…The best docked conformations were the lowest binding energy and the greatest number of conformations in the cluster (Healy et al, 2009). Amino acid residue within 6 Å of the ligand in the IN active site was chosen for H-bond interaction analysis using the HBond monitor in the DS Viewer Pro program (Roseau Valley, Dominica).…”

Section: Molecular Dockingmentioning

confidence: 99%

Anti-HIV-1 integrase activity and molecular docking of compounds fromAlbizia procerabark

Panthong

Bunluepuech

Boonnak

et al. 2015

Pharmaceutical Biology

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Context: Albizia procera (Roxb.) Benth. (Mimosaceae) has been traditionally used in Thai longevity preparations. Thus, searching for HIV-1 integrase (HIV-1 IN) agents from natural sources is of interest. Objective: The objective of this study is to examine the inhibitory activity against HIV-1 IN of compounds isolated from the stem bark of Albizia procera. Materials and methods: The EtOH extract and isolated compounds of Albizia procera bark were examined for anti-HIV-1 IN activity at various concentrations (10-100 mg/mL and 10-100 mM) using the multiplate integration assay and molecular docking. Results and discussions:The results showed that the ethanol extract had good anti-HIV-1 IN activity with an IC 50 value of 19.5 mg/mL, whereas ethyl acetate fraction exhibited the most potent with an IC 50 value of 19.1 mg/mL, followed by water fraction (IC 50 value ¼ 21.3 mg/mL), hexane and chloroform fractions (IC 50 value4100 mg/mL), respectively. From bioassay-guided isolation, the ethyl acetate fraction was further separated to give two compounds which are (+)-catechin (1) and protocatechuic acid (2), respectively. Of the tested samples, (+)-catechin (1) exhibited appreciable activity against HIV-1 IN with an IC 50 value of 46.3 mM, whereas protocatechuic acid (2) showed mild activity with 46.0% inhibition at concentration of 100 mM. (+)-Catechin (1) could interact with Thr66, Gly148, and Glu152 in the core domain of IN enzyme, whereas protocatechuic acid (2) could bind with Thr66, His67, Glu152, Asn155, and Lys159. This is the first report on anti-HIV-1 IN activity of Albizia procera bark. These results may suggest that Albizia procera bark has potential as anti-HIV-1 IN agent.

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“…14 One of the advantages of AutoDock allows a calculation of ∆Gbind and prediction of binding constants for docked igands. 11,13 ∆Gbind of the protein-ligand complex is simply calculated by the following equation (1).…”

Section: Resultsmentioning

confidence: 99%

“…Flexibilities of protein and ligand were incorporated in simulations and the binding free energies (∆Gbind) were estimated for the docked flavonoids. 11,13 The docking parameters included a trials of 100 dockings, random starting position and conformation, translation step ranges of 2 Å, rotation step ranges of 30°, mutation rate of 0.02, crossover rate of 0.8, 15 million energy evaluations, and a maximum 20,000 generation. More than 500 flavonoids from Indofine Chemical Company (Belle Mead, NJ) were included in our database.…”

Section: Methodsmentioning

confidence: 99%

Flavonoids can be Potent Inhibitors of Human Phenylethanolamine N-Methyltransferase (hPNMT)

Lee¹,

Jeong²,

Kim

2009

Bulletin of the Korean Chemical Society

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Inhibition of human phenylethanolamine N-methyltransferase (hPNMT) has been proposed as a method for the treatment of several mental processes which related on adrenaline metabolism. We performed in silico screening to identify flavonoid inhibitors of hPNMT using automated docking method and selected 9 inhibitor candidates based on ligand score (LigScore) and binding free energy (∆Gbind) estimation. Among 9 flavonoid candidates, 7 flavonoids belong to flavones while the rest of them belong to flavanone. All candidates have common chemical features; two hydrogen bond interactions with side chain of Lys75 and backbone carbonyl oxygen of Asn39, and two hydrophobic interactions. One hydrophobic site is formed by Val53, Leu262, and Met258 and the other is made up of Phe182, Ala186, Tyr222, and Val269. This study can be helpful to understand the structural features for inhibition of PNMT and showed flavonoids as promising inhibitor candidates for hPNMT.

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A docking study of l-chicoric acid with HIV-1 integrase

Cited by 37 publications

References 27 publications

Anti-HIV-1 integrase compounds from Dioscorea bulbifera and molecular docking study

Anti-HIV-1 integrase compounds from Dioscorea bulbifera and molecular docking study

Anti-HIV-1 integrase activity and molecular docking of compounds fromAlbizia procerabark

Flavonoids can be Potent Inhibitors of Human Phenylethanolamine N-Methyltransferase (hPNMT)

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