COX-2 structural analysis and docking studies with gallic acid structural analogues

Amaravani, M; Prasad, Nirmal K.; Vadde, Ramakrishna

doi:10.1186/2193-1801-1-58

Cited by 31 publications

(18 citation statements)

References 23 publications

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“…The carboxylic oxygen in dexibuprofen interacted with TYR295 at a bonding distance of 2.90 Å. The literature study also showed that binding pocket residues are common in our present result, which justified the significance of ligands binding [39]. …”

Section: Resultssupporting

confidence: 85%

Synthesis, Bioevaluation and Molecular Dynamic Simulation Studies of Dexibuprofen–Antioxidant Mutual Prodrugs

Ashraf

Alamgeer

Rasool

et al. 2016

IJMS

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Dexibuprofen–antioxidant conjugates were synthesized with the aim to reduce its gastrointestinal effects. The esters analogs of dexibuprofen 5a–c were obtained by reacting its –COOH group with chloroacetyl derivatives 3a–c. The in vitro hydrolysis data confirmed that synthesized prodrugs 5a–c were stable in stomach while undergo significant hydrolysis in 80% human plasma and thus release free dexibuprofen. The minimum reversion was observed at pH 1.2 suggesting that prodrugs are less irritating to stomach than dexibuprofen. The anti-inflammatory activity of 5c (p < 0.001) is more significant than the parent dexibuprofen. The prodrug 5c produced maximum inhibition (42.06%) of paw-edema against egg-albumin induced inflammation in mice. Anti-pyretic effects in mice indicated that prodrugs 5a and 5b showed significant inhibition of pyrexia (p < 0.001). The analgesic activity of 5a is more pronounced compared to other synthesized prodrugs. The mean percent inhibition indicated that the prodrug 5a was more active in decreasing the number of writhes induced by acetic acid than standard dexibuprofen. The ulcerogenic activity results assured that synthesized prodrugs produce less gastrointestinal adverse effects than dexibuprofen. The ex vivo antiplatelet aggregation activity results also confirmed that synthesized prodrugs are less irritant to gastrointestinal mucosa than the parent dexibuprofen. Molecular docking analysis showed that the prodrugs 5a–c interacts with the residues present in active binding sites of target protein. The stability of drug–target complexes is verified by molecular dynamic simulation study. It exhibited that synthesized prodrugs formed stable complexes with the COX-2 protein thus support our wet lab results. It is therefore concluded that the synthesized prodrugs have promising pharmacological activities with reduced gastrointestinal adverse effects than the parent drug.

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Section: Resultssupporting

confidence: 85%

Synthesis, Bioevaluation and Molecular Dynamic Simulation Studies of Dexibuprofen–Antioxidant Mutual Prodrugs

Ashraf

Alamgeer

Rasool

et al. 2016

IJMS

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“…Salicylic acid, which is released in body from salicin, is considered to have similar affinity toward COX-2 as acetylsalicylic acid. 21,22 Therefore, the secondary goal of this paper was to elucidate the interaction and binding affinity of salicin and COX-1 and COX-2 using molecular docking, an efficient tool to get an insight into ligand-receptor interactions. These molecular docking studies could be useful in better understanding of interactions between ligand and active sites of enzymes which is of great importance in aspect of designing a novel potent inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Methodological Aspects of Extraction, Phytochemical Characterization and Molecular Docking Studies of Salix caprea L. Bark and Leaves

Gligorić¹,

Igić²,

Suvajdžić³

et al. 2019

ACSi

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Contents of twelve selected bioactive substances and antioxidant potential of Salix caprea L. extracts were compared in its two vegetative organs (bark and leaves) and in terms of different ethanol/water mixtures used for extraction (30-70% aq, ethanol) and extraction time (30 min; 24, 48 and 72 h). The extracts were characterized by High Pressure Liquid Chromatography (HPLC), and total phenolics and flavonoids were determined spectrophotometrically. All secondary metabolites identified in Salix caprea L. extracts (gallic, chlorogenic and vanillic acid, epicatechin, rutin, quercetin and naringenin) were found more accumulated in bark. Salicin and p-hydroxybenzoic acid were detected in bark and ferulic, trans-cinnamic and p-coumaric acid in leaves extracts only. Rutin was most abundant bioactive compound both in bark (1.71 g/100 g of de) and leaves extracts (0.434 g/100 g of de). Bark extract with highest bioactive substances contents was obtained with 70% aq. ethanol as most suitable solvent during extraction time of 48 h. Molecular docking showed salicin to have similar affinity toward COX-2 as acetylsalicylic acid, but lower toward COX-1.

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“…2-(sulfooxy)benzoic acid possesses a structure similar to those of aspirin [2-(acetoxy)benzoic acid] and salicylic acid (2-hydroxybenzoic acid) ( Figure 6 ), which are potent analgesics and anti-inflammatory agents used for decades for treatment of various inflammatory conditions through inhibition of cyclooxygenases (COXs). Notably, it has been shown by molecular docking experiments, during the process of searching for analogues of gallic acid, a cyclooxygenase-2 (COX-2) inhibitor screened from medicinal plant, that 3-hydroxy-4-(sulfooxy)benzoic acid could be a potent COX-2 inhibitor [ 23 ]. However, both (sulfooxy)benzoic acid and hydroxy-(sulfooxy)benzoic acid have never been found naturally.…”

Section: Discussionmentioning

confidence: 99%

Metabolomics Analysis Reveals Specific Novel Tetrapeptide and Potential Anti-Inflammatory Metabolites in Pathogenic Aspergillus species

Lee

Tam

et al. 2015

IJMS

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Infections related to Aspergillus species have emerged to become an important focus in infectious diseases, as a result of the increasing use of immunosuppressive agents and high fatality associated with invasive aspergillosis. However, laboratory diagnosis of Aspergillus infections remains difficult. In this study, by comparing the metabolomic profiles of the culture supernatants of 30 strains of six pathogenic Aspergillus species (A. fumigatus, A. flavus, A. niger, A. terreus, A. nomius and A. tamarii) and 31 strains of 10 non-Aspergillus fungi, eight compounds present in all strains of the six Aspergillus species but not in any strain of the non-Aspergillus fungi were observed. One of the eight compounds, Leu–Glu–Leu–Glu, is a novel tetrapeptide and represents the first linear tetrapeptide observed in Aspergillus species, which we propose to be named aspergitide. Two other closely related Aspergillus-specific compounds, hydroxy-(sulfooxy)benzoic acid and (sulfooxy)benzoic acid, may possess anti-inflammatory properties, as 2-(sulfooxy)benzoic acid possesses a structure similar to those of aspirin [2-(acetoxy)benzoic acid] and salicylic acid (2-hydroxybenzoic acid). Further studies to examine the potentials of these Aspergillus-specific compounds for laboratory diagnosis of aspergillosis are warranted and further experiments will reveal whether Leu–Glu–Leu–Glu, hydroxy-(sulfooxy)benzoic acid and (sulfooxy)benzoic acid are virulent factors of the pathogenic Aspergillus species.

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COX-2 structural analysis and docking studies with gallic acid structural analogues

Cited by 31 publications

References 23 publications

Synthesis, Bioevaluation and Molecular Dynamic Simulation Studies of Dexibuprofen–Antioxidant Mutual Prodrugs

Synthesis, Bioevaluation and Molecular Dynamic Simulation Studies of Dexibuprofen–Antioxidant Mutual Prodrugs

Methodological Aspects of Extraction, Phytochemical Characterization and Molecular Docking Studies of Salix caprea L. Bark and Leaves

Metabolomics Analysis Reveals Specific Novel Tetrapeptide and Potential Anti-Inflammatory Metabolites in Pathogenic Aspergillus species

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