Modeling the binding modes of stilbene analogs to cyclooxygenase-2: a molecular docking study

Bouaziz-Terrachet, Souhila; Toumi-Maouche, Amel; Maouche, Boubekeur; Taïri-Kellou, Safia

doi:10.1007/s00894-010-0679-7

Cited by 29 publications

(9 citation statements)

References 47 publications

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“…The most known stilbene, resveratrol (trans-3,5,4′-trihydroxystilbene), demonstrates anti-inflammatory activity, but it has also been shown to be a non-selective inhibitor of COX-1 and COX-2. [20,21] Murias et al [22] described a series of hydroxylated resveratrol analogues selective COX-2 inhibitors with potency comparable to or better than the clinically established celecoxib; furthermore, more recently, Bouaziz-Terrachet et al [23] showed that a series of stilbene analogs is able to selectively inhibit COX-2. Interestingly this is the first report which describes naturally occurring dihydrostilbenes able to selectively inhibit COX-2.…”

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confidence: 99%

Selective COX-2 Inhibitory Properties of Dihydrostilbenes from Liquorice Leaves–In Vitro Assays and Structure/Activity Relationship Study

Trombetta

Giofrè

Tomaino

et al. 2014

Natural Product Communications

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Three dihydrostilbenes belonging to the polyphenol pool characterized in the leaves of Sicilian liquorice (Glycyrrhiza glabra L.) have been tested for their antioxidant and anti-inflammatory activity. The three dihydrostilbenes (PA-82, GA-23, DO-07) were in vitro tested to evaluate their capability to scavenge the stable radical 1,1-diphenyl-2-picrylhydrazyl (DPPH), and to decrease thromboxane B2 (TxB2) and prostaglandin E2 (PGE2) release in human whole blood samples. On the basis of the observed capability of these compounds to affect the cell COX-1/COX-2 pathway, a molecular docking study was carried out in order to understand in detail the ability of these compounds to bind to COX-1 and COX-2. The results show that the liquorice dihydrostilbenes are preferred ligands for COX-2 rather than for COX-1, providing a good rational for the observed selectivity in ex vivo experiments. Therefore, they appear to be good candidates for employment in human therapy against inflammation-related pathological conditions.

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confidence: 99%

Selective COX-2 Inhibitory Properties of Dihydrostilbenes from Liquorice Leaves–In Vitro Assays and Structure/Activity Relationship Study

Trombetta

Giofrè

Tomaino

et al. 2014

Natural Product Communications

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“…Such residues with higher binding energy contributions represented those contact points for electrostatic interactions, as described in molecular docking and Cα atom fluctuations. Similar information was described for the binding mode of stilbene analogs within the active site of COX-2 [35].…”

Section: Binding-free Energy Calculations Of the Best-docked 2-arylbementioning

confidence: 70%

Discrimination of Naturally-Occurring 2-Arylbenzofurans as Cyclooxygenase-2 Inhibitors: Insights into the Binding Mode and Enzymatic Inhibitory Activity

Coy-Barrera

2020

Biomolecules

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2-arylbenzofuran-containing compounds are chemical entities that can be naturally produced by several organisms. A wide-range of activities is described for several compounds of this kind and they are, therefore, valuable moieties for a lead finding from nature. Although there are in-vitro data about the activity of 2-arylbenzofuran-related compounds against cyclooxygenase (COX) enzymes, the molecular level of these COX-inhibiting constituents had not been deeply explored. Thus, 58 2-arylbenzofurans were initially screened through molecular docking within the active site of nine COX-2 crystal structures. The resulting docking scores were statistically analyzed and good reproducibility and convergence were found to discriminate the best-docked compounds. Discriminated compounds exhibited the best performance in molecular dynamics simulations as well as the most-favorable binding energies and the lowest in-vitro IC50 values for COX-2 inhibition. A three-dimensional quantitative activity-structure relationship (3D-QSAR) was also demonstrated, which showed some crucial structural requirements for enhanced enzyme inhibition. Therefore, four hits are proposed as lead structures for the development of COX-2 inhibitors based on 2-arylbenzofurans in further studies.

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“…Pocket S3 confined in the mouth of the active site and is delimited by Tyr355, Leu359, Val116 and Arg120. Shallow pocket S4 is localized in a hydrophobic area close to the hydrophobic pocket S2 which has a lesser number of residues, including Ile345, Leu534 and Leu531 . The inhibitors ( H 2 L and its complexes) were docked at the active site of COX‐2 and various interactions have been laid out (Figure ).…”

Section: Resultsmentioning

confidence: 86%

Synthesis, structural characterization and biological evaluation of mononuclear transition metal complexes of zwitterionic dehydroacetic acidN‐aroylhydrazone ligand

Kendur

Chimmalagi

Patil

et al. 2018

Applied Organom Chemis

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Synthesis and characterization of mononuclear transition metal complexes viz., Co(II), Ni(II), Cu(II) and Zn(II) with a newly designed ligand, (E)-2-benzamido-N'- (1-(2-hydroxy-6-methyl-4-oxo-4H-pyran-3-yl) ethylidene) benzohydrazide (H 2 L) are reported. Molecular structures of H 2 L, Ni(II) and Cu(II) complexes were determined by single-crystal X-ray diffraction studies. The structures were stabilized by various intra/inter-molecular H-bonding, C-H···π and π···π stacking interactions. H 2 L exists in zwitterionic form and acts in a monoanionic manner. Ligand/metal ratio was 2:1 for cobalt, nickel and zinc, whereas 1:1 for the copper complex. Co(II), Ni(II) and Zn(II) complexes display distorted octahedral geometry, while the Cu(II) complex shows distorted square pyramidal geometry around the metal ion. Hirshfeld surface analysis and 2D fingerprint plots revealed that H 2 L and its complexes were supported mainly by H⋯H, O⋯H and C⋯H intermolecular interactions. The synthesized compounds were screened for in vitro anti-inflammatory activity by gelatin zymography and the activity was comparable with tetracycline. Their cleavage behavior towards calf thymus DNA has been studied using agarose gel electrophoresis method. H 2 L and Cu(II) complex were selected by National Cancer Institute (NCI) for in vitro single dose testing in the full NCI 60 cell lines panel assay. Finally, molecular docking simulation effectively proves the binding of all the synthesized compounds at cyclooxygenase-2 (COX-2) active sites. KEYWORDS(E)-2-amino-N'-(1-(2-hydroxy-6-methyl-4-oxo-4H-pyran-3-yl)ethylidene) benzohydrazide, antiinflammatory and anticancer activity, molecular docking, single crystal X-ray diffraction study, transition metal complexes

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Modeling the binding modes of stilbene analogs to cyclooxygenase-2: a molecular docking study

Cited by 29 publications

References 47 publications

Selective COX-2 Inhibitory Properties of Dihydrostilbenes from Liquorice Leaves–In Vitro Assays and Structure/Activity Relationship Study

Selective COX-2 Inhibitory Properties of Dihydrostilbenes from Liquorice Leaves–In Vitro Assays and Structure/Activity Relationship Study

Discrimination of Naturally-Occurring 2-Arylbenzofurans as Cyclooxygenase-2 Inhibitors: Insights into the Binding Mode and Enzymatic Inhibitory Activity

Synthesis, structural characterization and biological evaluation of mononuclear transition metal complexes of zwitterionic dehydroacetic acidN‐aroylhydrazone ligand

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