Synthesis, evaluation and docking studies on 3-alkoxy-4-methanesulfonamido acetophenone derivatives as non ulcerogenic anti-inflammatory agents

Bali, Alka; Ohri, Ruchika; Deb, Pran Kishore

doi:10.1016/j.ejmech.2012.01.018

Cited by 25 publications

(12 citation statements)

References 19 publications

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“…The nonsteroidal antiinflammatory drugs (NSAIDs) are important therapeutic agents used for the treatment of pain and inflammation, act by reducing the production of proinflammatory prostaglandins (PGs) at the sites of injury via cyclooxygenase-2 (COX-2) inhibition 1,2 . It has been observed that COX isoenzymes exist in two different isoforms, a constitutive form (COX-1) and an inducible form (COX-2) 3 .…”

Section: Introductionmentioning

confidence: 99%

“…In contrast, the expression of COX-2 isozyme is rapidly induced by stimuli such as mitogenes and oncogenes, growth factors, hormones and disorders of water-electrolyte homeostasis linking its involvement to pathological processes such as inflammation and various cancer types [5][6][7] . The side effects associated with most of the NSAIDs such as gastrointestinal ulcer and renal function suppression are due to the inhibition of COX-1 pathway 1,2,8 . Thus the success of NSAIDs in treatment of various inflammatory disorders depends on the selective inhibition of COX-2 over COX-1 isoenzyme.…”

Section: Introductionmentioning

confidence: 99%

“…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. Earlier, a series of novel 6-substituted-2,3,4-trihydropyrimido[1,2c]9, 10,11,12-tetrahydrobenzo[b]thieno [3,2-e]pyrimidines (1)(2)(3)(4)(5)(6) have been synthesized and reported as antibacterial agents 11 . Interestingly, these compounds (1-6) also exhibited good antiinflammatory activity based on in silico docking studies using the COX-2 receptor.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Antiinflammatory Evaluation and Docking Studies of Some New Thienopyrimidines

Deb¹,

Maillabaram²,

Akkinepally³

et al. 2013

Asian J. Chem.

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“…CDX1 enantiomers interact through hydrogen bonds with His90, Leu352, Ser353, Tyr355, and Ala527, also involved in the binding of known anti-inflammatory compounds to COX-2 [48,49,50]. CDX1 enantiomers bind similarly to COX-2 binding pocket, with the xanthone scaffold aligned approximately in the same special position, with a slightly different orientation of the aromatic ring and OH group of the chiral moiety (Figure 2B).…”

Section: Resultsmentioning

confidence: 99%

Chiral Derivatives of Xanthones: Investigation of the Effect of Enantioselectivity on Inhibition of Cyclooxygenases (COX-1 and COX-2) and Binding Interaction with Human Serum Albumin

et al. 2017

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Searching of new enantiomerically pure chiral derivatives of xanthones (CDXs) with potential pharmacological properties, particularly those with anti-inflammatory activity, has remained an area of interest of our group. Herein, we describe in silico studies and in vitro inhibitory assays of cyclooxygenases (COX-1 and COX-2) for different enantiomeric pairs of CDXs. The evaluation of the inhibitory activities was performed by using the COX Inhibitor Screening Assay Kit. Docking simulations between the small molecules (CDXs; known ligands and decoys) and the enzyme targets were undertaken with AutoDock Vina embedded in PyRx—Virtual Screening Tool software. All the CDXs evaluated exhibited COX-1 and COX-2 inhibition potential as predicted. Considering that the (S)-(−)-enantiomer of the nonsteroidal anti-inflammatory drug ketoprofen preferentially binds to albumin, resulting in lower free plasma concentration than (R)-(+)-enantiomer, protein binding affinity for CDXs was also evaluated by spectrofluorimetry as well as in in silico. For some CDXs enantioselectivity was observed.

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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 docking studies on 3-alkoxy-4-methanesulfonamido acetophenone derivatives as non ulcerogenic anti-inflammatory agents

Cited by 25 publications

References 19 publications

Antiinflammatory Evaluation and Docking Studies of Some New Thienopyrimidines

Antiinflammatory Evaluation and Docking Studies of Some New Thienopyrimidines

Chiral Derivatives of Xanthones: Investigation of the Effect of Enantioselectivity on Inhibition of Cyclooxygenases (COX-1 and COX-2) and Binding Interaction with Human Serum Albumin

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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