Prediction of the Antiinflammatory Activity of New S-alkyl Derivatives of 1,2,4-triazol-3-thiones Using the PASS Computer Program and Molecular Docking

The strategy of rational approaches to the search for selective COX-2 inhibitors as potential antiinflammatory agents has been proposed and elaborated. It is based on the use of PASS-prediction and molecular docking. The choice of the basic structure of 4-amino-3-thio-1,2,4-triazole as a promising object of chemical modification has been substantiated. Using a modification of the primary molecule, a virtual library of S-derivatives of 5-substituted 4-amino(pyrrol)3-thio-4H-1,2,4-triazoles in the amount of 100 compounds (ten groups) has been obtained by introducing various pharmacophore fragments. Based on the analysis of the results of the PASS-prediction and molecular docking, six of the ten planned groups of compounds have been selected for the synthesis as promising selective COX-2 inhibitors. The reliability of the prediction results has already been confirmed for one of the promising group 4-amino-5-(pyridine-4-yl)-1,2,4-triazole (4?)-3-yl-thioacetamides.

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Design, syntheses, and evaluation of 2,3-diphenylcycloprop-2-en-1-ones and oxime derivatives as potential cyclooxygenase-2 (COX-2) inhibitors with analgesic-antiinflammatory activity

Drug Development Research ◽

10.1002/ddr.10102 ◽

2002 ◽

Vol 57 (1) ◽

pp. 6-17 ◽

Cited By ~ 7

Author(s):

Huiying Li ◽

P.N. Praveen Rao ◽

Amgad G. Habeeb ◽

Edward E. Knaus

Keyword(s):

Antiinflammatory Activity ◽

Cyclooxygenase 2 ◽

Cox 2 ◽

Oxime Derivatives ◽

Cox 2 Inhibitors

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Design, Synthesis, Molecular Docking and Biological Evaluation of Novel Coumarin-Oxime Ether Derivatives as COX-2 Inhibitors

Asian Journal of Chemistry ◽

10.14233/ajchem.2017.20865 ◽

2017 ◽

Vol 29 (11) ◽

pp. 2559-2564

Author(s):

M. Vijaya Bhargavi ◽

P. Shashikala ◽

M. Sumakanth ◽

Shravan Kumar Gunda

Keyword(s):

Molecular Docking ◽

Biological Evaluation ◽

Oxime Ether ◽

Design Synthesis ◽

Cox 2 ◽

Cox 2 Inhibitors

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A One-Pot Multicomponent Catalytic Synthesis of New 1H-Pyrazole-1-Carbothioamide Derivatives with Molecular Docking Studies as COX-2 Inhibitors

Biointerface Research in Applied Chemistry ◽

10.33263/briac116.1377913789 ◽

2021 ◽

Vol 11 (6) ◽

pp. 13779-13789

Keyword(s):

Molecular Docking ◽

Simple Procedure ◽

Docking Studies ◽

Catalytic Synthesis ◽

One Pot ◽

Reference Drug ◽

Molecular Docking Studies ◽

Wide Range ◽

Cox 2 ◽

Cox 2 Inhibitors

A simple and efﬁcient catalytic synthesis of new 1H-pyrazole-1-carbothioamide derivatives through a one-pot reaction of hydrazine hydrate, arylidene malononitrile and isothiocyanates in the presence of HAp/ZnCl2 nano-flakes at 60-70°C has been described. The protocol's main advantages include high yields of products, a wide range of substrates, simple procedure, and short reaction time. Molecular docking studies of the designed compounds were accomplished as COX-2 inhibitors and showed that compounds 3d, 3e, 3h, and 3n give promising results compared with celecoxib as a reference drug.

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Synthesis, biological evaluation and molecular docking studies of stellatin derivatives as cyclooxygenase (COX-1, COX-2) inhibitors and anti-inflammatory agents

Bioorganic & Medicinal Chemistry Letters ◽

10.1016/j.bmcl.2011.01.116 ◽

2011 ◽

Vol 21 (6) ◽

pp. 1612-1616 ◽

Cited By ~ 38

Author(s):

Raju Gautam ◽

Sanjay M. Jachak ◽

Vivek Kumar ◽

C. Gopi Mohan

Keyword(s):

Molecular Docking ◽

Docking Studies ◽

Biological Evaluation ◽

Molecular Docking Studies ◽

Cox 2 ◽

Anti Inflammatory ◽

Cox 2 Inhibitors ◽

Cox 1

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Design, Synthesis and Comprehensive Investigations of Pyrrolo[3,4-d]pyridazinone-Based 1,3,4-Oxadiazole as New Class of Selective COX-2 Inhibitors

International Journal of Molecular Sciences ◽

10.3390/ijms21249623 ◽

2020 ◽

Vol 21 (24) ◽

pp. 9623

Author(s):

Łukasz Szczukowski ◽

Edward Krzyżak ◽

Adrianna Zborowska ◽

Patrycja Zając ◽

Katarzyna Potyrak ◽

...

Keyword(s):

Molecular Docking ◽

Docking Studies ◽

One Pot ◽

Design Synthesis ◽

Biological Studies ◽

Cox 2 ◽

Anti Inflammatory ◽

Dna Strand ◽

Cox 2 Inhibitors

The long-term use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in treatment of different chronic inflammatory disorders is strongly restricted by their serious gastrointestinal adverse effects. Therefore, there is still an urgent need to search for new, safe, and efficient anti-inflammatory agents. Previously, we have reported the Mannich base-type derivatives of pyrrolo[3,4-d]pyridazinone which strongly inhibit cyclooxygenase, have better affinity to COX-2 isoenzyme and exert promising anti-oxidant activity. These findings encouraged us to perform further optimization of that structure. Herein, we present the design, synthesis, molecular docking, spectroscopic, and biological studies of novel pyrrolo[3,4-d]pyridazinone derivatives bearing 4-aryl-1-(1-oxoethyl)piperazine pharmacophore 5a,b–6a,b. The new compounds were obtained via convenient, efficient, one-pot synthesis. According to in vitro evaluations, novel molecules exert no cytotoxicity and act as selective COX-2 inhibitors. These findings stay in good correlation with molecular modeling results, which additionally showed that investigated compounds take a position in the active site of COX-2 very similar to Meloxicam. Moreover, all derivatives reduce the increased level of reactive oxygen and nitrogen species and prevent DNA strand breaks caused by oxidative stress. Finally, performed spectroscopic and molecular docking studies demonstrated that new compound interactions with bovine serum albumin (BSA) are moderate, formation of complexes is in one-to-one ratio, and binding site II (subdomain IIIA) is favorable.

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