Molecular modeling, synthesis and screening of some new 4-thiazolidinone derivatives with promising selective COX-2 inhibitory activity

Tan, Oya Ünsal; Özadalı, Keriman; Piskin, K.; Balkan, Ayla

doi:10.1016/j.ejmech.2012.08.046

Cited by 64 publications

(29 citation statements)

References 16 publications

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“…The effect of the compounds on ovine COX‐1 and human recombinant COX‐2 (IC 50 value, µM) enzymes were determined by measuring prostaglandin F2α (PGF2α) using a COX Inhibitor Screening Kit (Catalog No 560131 from Cayman Chemical, Ann Arbor, MI) following the procedure suggested by manufacturer. The IC 50 values (the concentration of the test compound causing 50% inhibition) were calculated from the concentration‐inhibition response curves (duplicate determinations) .…”

Section: Methodsmentioning

confidence: 99%

Design, Synthesis and In Vitro Study of 5,6‐Diaryl‐1,2,4‐triazine‐3‐ylthioacetate Derivatives as COX‐2 and β‐Amyloid Aggregation Inhibitors

Dadashpour

Küçükkılınç

Tan

et al. 2015

Archiv der Pharmazie

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In order to find novel cyclooxygenase (COX)-2 inhibitors for treating inflammatory-based diseases such as Alzheimer's disease (AD), an ethyl carboxylate side chain was added to 5-(4-chlorophenyl)-6-(4-(methylsulfonyl)phenyl)-3-(methylthio)-1,2,4-triazine (lead compound II) to maintain residual inhibition of COX-1 through interacting with Arg120. A preliminary molecular docking study on both the COX-1/COX-2 active sites truly confirmed our hypothesis. Accordingly, a series of ethyl 5,6-diaryl-1,2,4-triazine-3-ylthioacetate derivatives were synthesized and their chemical structures were confirmed by NMR, IR and MS spectra. Further in vitro COX-1/COX-2 evaluations revealed that compound 6c (COX-2 IC50 = 10.1 μM, COX-1 IC50 = 88.8 μM) is the most selective COX-2 inhibitor while maintaining residual inhibition of COX-1. In order to evaluate their potential use against AD, an in vitro evaluation of β-amyloid fibril formation was performed. The results indicated that the prototype compounds 6 are effective β-amyloid destabilizing agents while compound 6c could inhibit 94% of the β-amyloid fibril formation after 48 h. Finally, the in silico assessment results of their blood-brain barrier permeability were satisfactory.

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Section: Methodsmentioning

confidence: 99%

Design, Synthesis and In Vitro Study of 5,6‐Diaryl‐1,2,4‐triazine‐3‐ylthioacetate Derivatives as COX‐2 and β‐Amyloid Aggregation Inhibitors

Dadashpour

Küçükkılınç

Tan

et al. 2015

Archiv der Pharmazie

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“…On the other hand, thiazole‐based compounds received considerable attention owing to their high anti‐inflammatory potential. Diversely substituted thiazole derivatives showed potent selective COX‐2 inhibitory properties.…”

Section: Introductionmentioning

confidence: 99%

New Coumarin Derivatives as Potent Selective COX‐2 Inhibitors: Synthesis, Anti‐Inflammatory, QSAR, and Molecular Modeling Studies

Dawood

Batran

Farghaly

et al. 2015

Archiv der Pharmazie

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Two new series of coumarin derivatives incorporating thiazoline and thiazolidinone moieties were designed, synthesized, and investigated in vivo for their anti-inflammatory activities using the carrageenan-induced rat paw edema model and in vitro for their inhibitory activities against the human cyclooxygenase (COX)-1 and COX-2 isoforms. Most of the synthesized compounds demonstrated exceptionally high in vivo anti-inflammatory activity and displayed superior GI safety profiles (0-7% ulceration) as compared to indomethacin. All the bioactive compounds showed in vitro high affinity and selectivity toward the COX-2 isoenzyme, compared to the reference celecoxib with IC50 values ranging from 0.31 to 0.78 μM. The ethyl thiosemicarbazone 2b, thiazoline derivatives 3a, 3b, 5b, 6a, and 7f, and the thiazolidinone compounds 8b and 9a showed the highest in vivo and in vitro anti-inflammatory activities with remarkable COX-2 selectivity. Quantitative structure-activity relationship study (QSAR) was done and resulted in a highly predictive power R(2) (0.908). A molecular docking study revealed a relationship between the docking affinity and the biological results.

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“…Several compounds of this family shows diverse biological activities such as anti‐histaminic, anti‐hypersensitive, anti‐cancer and anti‐oxidants etc . The potent activity as a non‐nucleoside inhibitor of the hepatitis C virus showed by compound 1 , compound 2 reported as selective HIV‐1 reverse transcriptase inhibitors and compound 3 display high COX‐2 inhibitor . Further, the recent report mentioned that the toxicologically of 4‐thiazolidinone derivatives are genotoxically safe .…”

Section: Introductionmentioning

confidence: 99%

Selective and Solvent‐Free Synthesis of Isoxazole‐Containing Spiro‐Thiazolidinones Using TiO₂‐SO₃H as Solid Catalyst

Singh

Bhardwaj

2019

ChemistrySelect

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A solvent‐free nano‐titania‐supported sulfonic acid [nano‐TiO2‐SO3H (n‐TSA)] catalyzed approach has been developed for the synthesis of pharmaceutically interesting new hybrids of isoxazolyl‐spiro‐thiazolidinones. The key feature of present investigated three component reaction of cyclic ketones (isatin, ninhydrin and acenaphthenequinone), 3‐amino‐5‐methyl‐isoxazole and α‐mercaptocarboxylic acids involves the synthesis of a five member ring system instead of the anticipated seven member ring system & also exploits the possibility of other likely isomers, regio and diastereoselectively. The selectivity of synthesized spiro‐thiazolidinone systems was established, based on the spectroscopic outcome and single crystal X‐ray analyses of representative compounds. Further, the use of a solid catalyst, n‐TSA under solvent‐free conditions was observed to be the best choice of reaction conditions, as it not only afforded the product in higher yields in less reaction time but in an environmentally friendly manner as well.

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Molecular modeling, synthesis and screening of some new 4-thiazolidinone derivatives with promising selective COX-2 inhibitory activity

Cited by 64 publications

References 16 publications

Design, Synthesis and In Vitro Study of 5,6‐Diaryl‐1,2,4‐triazine‐3‐ylthioacetate Derivatives as COX‐2 and β‐Amyloid Aggregation Inhibitors

Design, Synthesis and In Vitro Study of 5,6‐Diaryl‐1,2,4‐triazine‐3‐ylthioacetate Derivatives as COX‐2 and β‐Amyloid Aggregation Inhibitors

New Coumarin Derivatives as Potent Selective COX‐2 Inhibitors: Synthesis, Anti‐Inflammatory, QSAR, and Molecular Modeling Studies

Selective and Solvent‐Free Synthesis of Isoxazole‐Containing Spiro‐Thiazolidinones Using TiO₂‐SO₃H as Solid Catalyst

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Molecular modeling, synthesis and screening of some new 4-thiazolidinone derivatives with promising selective COX-2 inhibitory activity

Cited by 64 publications

References 16 publications

Design, Synthesis and In Vitro Study of 5,6‐Diaryl‐1,2,4‐triazine‐3‐ylthioacetate Derivatives as COX‐2 and β‐Amyloid Aggregation Inhibitors

Design, Synthesis and In Vitro Study of 5,6‐Diaryl‐1,2,4‐triazine‐3‐ylthioacetate Derivatives as COX‐2 and β‐Amyloid Aggregation Inhibitors

New Coumarin Derivatives as Potent Selective COX‐2 Inhibitors: Synthesis, Anti‐Inflammatory, QSAR, and Molecular Modeling Studies

Selective and Solvent‐Free Synthesis of Isoxazole‐Containing Spiro‐Thiazolidinones Using TiO2‐SO3H as Solid Catalyst

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Selective and Solvent‐Free Synthesis of Isoxazole‐Containing Spiro‐Thiazolidinones Using TiO₂‐SO₃H as Solid Catalyst