Synthesis, biological evaluation and docking study of maleimide derivatives bearing benzenesulfonamide as selective COX-2 inhibitors and anti-inflammatory agents

Firke, Sandip D.; Bari, Sanjay B.

doi:10.1016/j.bmc.2015.07.070

Cited by 43 publications

(16 citation statements)

References 34 publications

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“…To find the potential bioactive conformation of the thieno[3,2-c]pyran analogs, the SYBYL-X 2.1.1 suite with the Geom-X mode of the Surflex-Dock engine was used to perform the molecular docking simulation. Thieno[3,2-c]pyran analogs were used as ligands, and SIRT6 (PDB ID: 3K35) 69 and COX-2 (PDB ID: 6COX) 70 were used as a potential drug targets. The standard protocol was adopted for protein preparation before docking; i.e.…”

Section: Methodsmentioning

confidence: 99%

Molecular Insights into the Interaction of RONS and Thieno[3,2-c]pyran Analogs with SIRT6/COX-2: A Molecular Dynamics Study

Yadav

Kumar

Saloni

et al. 2018

Sci Rep

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SIRT6 and COX-2 are oncogenes target that promote the expression of proinflammatory and pro-survival proteins through a signaling pathway, which leads to increased survival and proliferation of tumor cells. However, COX-2 also suppresses skin tumorigenesis and their relationship with SIRT6, making it an interesting target for the discovery of drugs with anti-inflammatory and anti-cancer properties. Herein, we studied the interaction of thieno[3,2-c]pyran analogs and RONS species with SIRT6 and COX-2 through the use of molecular docking and molecular dynamic simulations. Molecular docking studies revealed the importance of hydrophobic and hydrophilic amino acid residues for the stability. The molecular dynamics study examined conformational changes in the enzymes caused by the binding of the substrates and how those changes affected the stability of the protein-drug complex. The average RMSD values of the backbone atoms in compounds 6 and 10 were calculated from 1000 ps to 10000 ps and were found to be 0.13 nm for both compounds. Similarly, the radius of gyration values for compounds 6 and 10 were found to be 1.87 ± 0.03 nm and 1.86 ± 0.02 nm, respectively. The work presented here, will be of great help in lead identification and optimization for early drug discovery.

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Section: Methodsmentioning

confidence: 99%

Molecular Insights into the Interaction of RONS and Thieno[3,2-c]pyran Analogs with SIRT6/COX-2: A Molecular Dynamics Study

Yadav

Kumar

Saloni

et al. 2018

Sci Rep

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“…Nitrogen heterocyclic moieties such as pyrazoles and pyrimidines containing derivatives gained considerable attention in medicinal chemistry for their broad-spectrum pharmacological activities such as antimicrobial, anti-inflammatory, analgesic, enzyme inhibition, antioxidant, and anticancer. These moieties have leading position in drug designing as important pharmacophore [10][11][12][13][14][15] .…”

Section: Introductionmentioning

confidence: 99%

Screening of curcumin‐derived isoxazole, pyrazoles, and pyrimidines for their anti‐inflammatory, antinociceptive, and cyclooxygenase‐2 inhibition

et al. 2017

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Curcumin has shown pharmacological properties against different phenotypes of various disease models. Different synthetic routes have been employed to develop its numerous derivatives for diverse and improved therapeutic roles. In this study, we have synthesized curcumin derivatives containing isoxazole, pyrazoles, and pyrimidines and then the synthesized molecules were evaluated for their anti-inflammatory and antinociceptive activities in experimental animal models. Acute toxicity of synthesized molecules was evaluated in albino mice by oral administration. Any behavioral and neurological changes were observed at dose of 10 mg/kg body weight.Additionally, cyclooxygenase-2 (COX-2) enzyme inhibition studies were performed through in vitro assays. In vivo anti-inflammatory studies showed that curcumin with pyrimidines was the most potent anti-inflammatory agent which inhibited induced edema from 74.7% to 75.9%. Compounds 7, 9, and 12 exhibited relatively higher prevention of writhing episodes than any other compound with antinociceptive activity of 73.2%, 74.9%, and 71.8%, respectively. This was better than diclofenac sodium (reference drug, 67.1% inhibition). Similarly, COX-2 in vitro inhibition assays results revealed that compound 12 (75.3% inhibition) was the most potent compound.Molecular docking studies of 10, 11, and 12 compounds in human COX-2 binding site revealed the similar binding modes as that of other COX-2-selective inhibitors. K E Y W O R D Santi-inflammatory, COX-2 inhibition, curcumin derivatives, molecular modeling Chemically curcumin is diferuloylmethane which has attracted much attention of medicinal chemists for various diseases and therapeutic agents development. It has shown its pharmacological safety and wide range of biological activities such as antibacterial to anticancer agent [1][2][3][4] . Currently, curcumin is acclaimed to be one of the most widely researched naturally occurring chemopreventive agent which is cytoprotective to healthy human cells [5][6][7] . In spite of important therapeutic application, limited therapeutic utility concerns are associated with curcumin because of its poor absorption and fast metabolism under physiological conditions [8] . Active methylene and keto moiety are believed to be responsible for its rapid metabolism. In order to circumvent the problem of rapid metabolism and to improve its pharmacokinetics profile, several synthetic modifications have been studied on carbonyl and active methylene moiety [9] . In present study, isoxazole, N-substituted pyrazoles, and pyrimidine ring were incorporated in this focused segment of curcumin. Nitrogen heterocyclic moieties such as pyrazoles and pyrimidines containing derivatives gained considerable attention in medicinal chemistry for

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“…10). 47 The majority of selective COX-2 inhibitors belong to diarylheterocycles that contain vicinal diaryl substituents attached to a central ring system, mainly a mono-or bicyclic ring. A particular class is represented by 3′-(4-substituted phenyl)-4′-(4-(methylsulfonyl)phenyl)spiroisoxazoline This journal is © The Royal Society of Chemistry derivatives containing naphthalene and chromanonespirobridges.…”

Section: Introductionmentioning

confidence: 99%

Structure–activity relationships for the synthesis of selective cyclooxygenase 2 inhibitors: an overview (2009–2016)

2017

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Most drugs used to treat pain and inflammation act through inhibition of the enzymes prostaglandin G/H synthase, commonly known as cyclooxygenase (COX). Among these, the simultaneous inhibition of cyclooxygenase 1 (COX-1) would explain the unwanted side effects in the gastrointestinal tract and many adverse cardiovascular effects, such as high blood pressure, myocardial infarction and thrombosis. These side effects led in time to the development of NSAIDs that behave as selective COX-2 inhibitors. This manuscript highlights the structure-activity relationships which characterize the chemical scaffolds endowed with selective COX-2 inhibition. Additionally, the role of COX-2 inhibitors in the pain phenomenon and cancer is discussed.

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Synthesis, biological evaluation and docking study of maleimide derivatives bearing benzenesulfonamide as selective COX-2 inhibitors and anti-inflammatory agents

Cited by 43 publications

References 34 publications

Molecular Insights into the Interaction of RONS and Thieno[3,2-c]pyran Analogs with SIRT6/COX-2: A Molecular Dynamics Study

Molecular Insights into the Interaction of RONS and Thieno[3,2-c]pyran Analogs with SIRT6/COX-2: A Molecular Dynamics Study

Screening of curcumin‐derived isoxazole, pyrazoles, and pyrimidines for their anti‐inflammatory, antinociceptive, and cyclooxygenase‐2 inhibition

Structure–activity relationships for the synthesis of selective cyclooxygenase 2 inhibitors: an overview (2009–2016)

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