Synthesis, evaluation, and molecular docking studies of cycloalkyl/aryl-3,4,5-trimethylgallates as potent non-ulcerogenic and gastroprotective anti-inflammatory agents

Dhingra, Mamta Sachdeva; Deb, Pran Kishore; Chadha, Renu; Singh, Tejvir; Karan, Maninder

doi:10.1007/s00044-013-0620-6

Cited by 17 publications

(10 citation statements)

References 45 publications

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“…These amino acid similarities indicate that xanthones are able to occupy the active site of the COX-2 enzyme, and are believed to engage ininhibitory activity against the COX-2 enzyme. 385 , and Ser 53° are also associated with better COX-2 inhibitory activity [46].…”

Section: Docking Molecular Of Celecoxib Against Cox-1 and Cox-2 Enzymesmentioning

confidence: 99%

In Silico Molecular Docking of Xanthone Derivatives as Cyclooxygenase-2 Inhibitor Agents

Miladiyah

Jumina

Haryana

et al. 2017

Int J Pharm Pharm Sci

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Objective: To demonstrate the potential ofdifferent xanthone derivatives as cyclooxygenase-2 (COX-2) inhibitor agents and their selectivity against cycloooxygenase-1 (COX-1) and COX-2 using molecular simulation. Methods:Nine novel xanthone derivatives (compounds A-I) were employed to dock against protein COX-2 (Protein Data Bank/PDB ID: 1CX2) and COX-1 (PDB ID: 3N8Z). Celecoxib, a selective COX-2 inhibitor, was chosen as a control compound. The free binding energy produced by the docking was scored using Protein-Ligand Ant System (PLANTS) and the hydrogen bonds (H-bonds) between ligands and enzymes were visualised using Pymol.Results: Molecular docking studies revealed that celecoxib docked to the active site of COX-2 enzyme, but not to COX-1; where as xanthone derivatives docked to the active site of both COX-2 and COX-1. Free binding energy of xanthone derivatives ranged between-73, 57 to-79,18 and between-73,06 to-79,25 against COX-2 and COX-1, respectively, and-78,13 against celecoxib. H-bonds in the molecule of xanthone derivatives and COX-2 protein were found in amino acid residues Arg 120 , Tyr 355 , Tyr 385 , and Ser 353 . There was an insignificant difference between the free binding energyof xanthone derivatives against COX-2 and against COX-1, suggesting that their inhibition was non-selective. Conclusion:In conclusion, in silico studies showed that xanthone derivatives could be effective as potential inhibitors against COX-2, although they are not selective.

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Section: Docking Molecular Of Celecoxib Against Cox-1 and Cox-2 Enzymesmentioning

confidence: 99%

In Silico Molecular Docking of Xanthone Derivatives as Cyclooxygenase-2 Inhibitor Agents

Miladiyah

Jumina

Haryana

et al. 2017

Int J Pharm Pharm Sci

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“…Thus the success of NSAIDs in treatment of various inflammatory disorders depends on the selective inhibition of COX-2 over COX-1 isoenzyme. Failure of some COXIBs such as rofecoxib due to its adverse cardiovascular side effects 9 imposed a great challenge to the researchers to explore and evaluate alternative templates with selective COX-2 inhibitory activity 10 . Recently, a series of 8/ 10-trifluo-romethyl-substituted-imidazo[1,2-c]quinazolines 2 , 3-alkoxy-4-methanesulfonamido acetophenone derivatives1 cycloalkyl/aryl-3,4,5-trimethylgallates 10 have been reported from our laboratory as potent antiinflammatory agents.…”

Section: Introductionmentioning

confidence: 99%

Antiinflammatory Evaluation and Docking Studies of Some New Thienopyrimidines

Deb¹,

Maillabaram²,

Akkinepally³

et al. 2013

Asian J. Chem.

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A series of some new 6-substituted-2,3,4-trihydropyrimido [1,2-c]9,10,11,12-tetrahydrobenzo[b]thieno[3,2-e]pyrimidines (1-6) have been evaluated in silico (docking studies) to recognize their hypothetical binding motif with the cyclooxygenase isoenzyme (COX-2) employing GLIDE software (Schrodinger Inc.) and in vivo (rat paw edema) for their antiinflammatory activities. The compound 6 with pyridyl substitution at the 6 th position of the thienopyrimidine moiety was found to form significant H-bonding interaction with crucial amino acid residue Arg 120 at a distance of 3 Å and exhibited good antiinflammatory activity [around 87 % of the standard: indomethacin]. The binding mode of the thienopyrimidines compounds have been proposed based on the docking studies. Further, the predicted ADME properties of all the tested compounds were found to be in the ranges as predicted by QikProp for 95 % of known oral drugs and also satisfy the Lipinski's rule of five.

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“…Several atempts were made to extensively manipulate the ring system that is fused with the cis-stilbene system to include every possible heterocyclic ring of varying sizes as well as by altering the scafolds of classical NSAIDs to convert them into COX-2 selective inhibitors, but none could successfully reach the market. Recently, a series of thiazole derivatives [21], cycloalkyl/aryl-3,4,5-trimethylgallates [22], thienopyrimidine derivatives [23], 3-alkoxy-4-methanesulfonamido acetophenone derivatives [24] and 8/10-triluoromethyl-substituted-imidazo[1,2-c]quinazolines [25], have been designed, synthesised and reported from our research group in search of compounds with novel scafold as potent anti-inlammatory agents.…”

Section: Progress In the Pursuit Of The Development Of Cyclooxygenasementioning

confidence: 99%

Molecular Basis of Binding Interactions of NSAIDs and Computer-Aided Drug Design Approaches in the Pursuit of the Development of Cyclooxygenase-2 (COX-2) Selective Inhibitors

Deb¹,

Mailabaram²,

Al-Jaidi³

et al. 2017

Nonsteroidal Anti-Inflammatory Drugs

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The nonsteroidal anti-inlammatory drugs (NSAIDs) are important class of therapeutic agents used for the treatment of pain, inlammation and fever. Nonselective inhibition of cyclooxygenase (COX-1 and COX-2) isoenzymes by classical NSAIDs is associated with undesirable side efects such as gastrointestinal (GI) and renal toxicities due to COX-1 inhibition. To circumvent this problem, several COX-2 selective inhibitors were developed with superior GI safety proile. However, the voluntary market withdrawal of potent COX-2 selective inhibitors (rofecoxib and valdecoxib) due to their severe cardiovascular toxicity which is also found to be associated with some of the traditional NSAIDs suggesting the need to relook into the entire class of NSAIDs rather than exclusively victimizing the COX-2 selective inhibitors. Furthermore, the recent evidences for the involvement of COX-2 selective inhibitors in the aetiology of many diseases, such as Alzheimer's disease, Parkinson's disease, diabetes, various cancers and so on, have gained much atention for researchers to design and develop novel COX-2 selective inhibitors with improved pharmacodynamics and pharmacokinetic proile. This chapter is focused on the detailed analysis of molecular basis of binding interactions of various NSAIDs by highlighting the role of crucial amino acid residues at the binding site of cyclooxygenase enzymes (COXs) to be considered for selective inhibition of COX-2 enzyme while emphasising the impact of signiicant CADD strategies employed for designing new potent COX-2 inhibitors with tuned selectivity.

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Synthesis, evaluation, and molecular docking studies of cycloalkyl/aryl-3,4,5-trimethylgallates as potent non-ulcerogenic and gastroprotective anti-inflammatory agents

Cited by 17 publications

References 45 publications

In Silico Molecular Docking of Xanthone Derivatives as Cyclooxygenase-2 Inhibitor Agents

In Silico Molecular Docking of Xanthone Derivatives as Cyclooxygenase-2 Inhibitor Agents

Antiinflammatory Evaluation and Docking Studies of Some New Thienopyrimidines

Molecular Basis of Binding Interactions of NSAIDs and Computer-Aided Drug Design Approaches in the Pursuit of the Development of Cyclooxygenase-2 (COX-2) Selective Inhibitors

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