Molecular Docking, Synthesis, and, Biological Activity of New Diclofenac Derivatives Incorporating 1,2,4-Triazole Ring as a Promising Antibacterial Agents

NSAIDs, recently have been shown to exert a wide variety of biological activities, such as antibacterial, antifungal, antioxidant, and anticancer activity. The triazole ring has various pharmacological activities of tetrazole ring, anticancer, antidiabetic, antifungal, antioxidant, anticonvulsant,...

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Main Authors: Alyaa N. Doohee, Noor H. Naser, Karrar AL-GBURI
Format: Article
Language:English
Published: College of Pharmacy University of Baghdad 2025-03-01
Series:Iraqi Journal of Pharmaceutical Sciences
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Online Access:https://bijps.uobaghdad.edu.iq/index.php/bijps/article/view/2934
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author Alyaa N. Doohee
Noor H. Naser
Karrar AL-GBURI
author_facet Alyaa N. Doohee
Noor H. Naser
Karrar AL-GBURI
author_sort Alyaa N. Doohee
collection DOAJ
description NSAIDs, recently have been shown to exert a wide variety of biological activities, such as antibacterial, antifungal, antioxidant, and anticancer activity. The triazole ring has various pharmacological activities of tetrazole ring, anticancer, antidiabetic, antifungal, antioxidant, anticonvulsant, antiviral, and antibacterial properties. Hence, the aim of this study was to design, synthesize, molecular docking, and assess the antibacterial activity of new diclofenac derivatives incorporating a 1,2,4-triazole ring. Molecular docking studies were carried out using MOE 2015 software using a standard protocol. The new diclofenac derivatives (VIa-d) were synthesized by esterifying diclofenac, reacting the product with hydrated hydrazine and carbon disulfide, and cyclization to form a 1,2,4-triazole ring. Finally, the reaction of the benzoyl chloride derivatives with the primary amino group on the synthesized triazole ring via a nucleophilic substitution reaction. In vitro antibacterial activity of diclofenac, and the synthesized compounds were evaluated by using the agar-well diffusion method. Compounds (VIa-d) have shown a higher binding score than the reference ligand (Topotecan) against Human DNA topoisomerase I (PDB: 1K4T), while they were nearly identical to the reference ligand (levofloxacin) against type IV topoisomerase from S. pneumoniae (PDB: 3RAE).  All of the compounds inhibited growth of the Staphylococcus aureus and Escherichia coli, with compound VId exhibiting the highest level of activity.
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spelling doaj-art-e66b1d026ace423e941eb57433e572c72025-08-20T02:10:19ZengCollege of Pharmacy University of BaghdadIraqi Journal of Pharmaceutical Sciences1683-35972521-35122025-03-0134110.31351/vol34iss1pp165-175Molecular Docking, Synthesis, and, Biological Activity of New Diclofenac Derivatives Incorporating 1,2,4-Triazole Ring as a Promising Antibacterial AgentsAlyaa N. Doohee0Noor H. Naser1Karrar AL-GBURI2Department of Pharmaceutical Chemistry, College of Pharmacy, Al-Zahraa University for Women, Holy Karbala, Iraq. Department of Pharmaceutical Chemistry, College of Pharmacy, Al-Zahraa University for Women, Holy Karbala, IraqDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Kufa, Najaf, Iraq NSAIDs, recently have been shown to exert a wide variety of biological activities, such as antibacterial, antifungal, antioxidant, and anticancer activity. The triazole ring has various pharmacological activities of tetrazole ring, anticancer, antidiabetic, antifungal, antioxidant, anticonvulsant, antiviral, and antibacterial properties. Hence, the aim of this study was to design, synthesize, molecular docking, and assess the antibacterial activity of new diclofenac derivatives incorporating a 1,2,4-triazole ring. Molecular docking studies were carried out using MOE 2015 software using a standard protocol. The new diclofenac derivatives (VIa-d) were synthesized by esterifying diclofenac, reacting the product with hydrated hydrazine and carbon disulfide, and cyclization to form a 1,2,4-triazole ring. Finally, the reaction of the benzoyl chloride derivatives with the primary amino group on the synthesized triazole ring via a nucleophilic substitution reaction. In vitro antibacterial activity of diclofenac, and the synthesized compounds were evaluated by using the agar-well diffusion method. Compounds (VIa-d) have shown a higher binding score than the reference ligand (Topotecan) against Human DNA topoisomerase I (PDB: 1K4T), while they were nearly identical to the reference ligand (levofloxacin) against type IV topoisomerase from S. pneumoniae (PDB: 3RAE).  All of the compounds inhibited growth of the Staphylococcus aureus and Escherichia coli, with compound VId exhibiting the highest level of activity. https://bijps.uobaghdad.edu.iq/index.php/bijps/article/view/2934DiclofenacMolecular Docking1,2,4-triazoleantibacterial activitybenzoyl chloride derivatives
spellingShingle Alyaa N. Doohee
Noor H. Naser
Karrar AL-GBURI
Molecular Docking, Synthesis, and, Biological Activity of New Diclofenac Derivatives Incorporating 1,2,4-Triazole Ring as a Promising Antibacterial Agents
Iraqi Journal of Pharmaceutical Sciences
Diclofenac
Molecular Docking
1,2,4-triazole
antibacterial activity
benzoyl chloride derivatives
title Molecular Docking, Synthesis, and, Biological Activity of New Diclofenac Derivatives Incorporating 1,2,4-Triazole Ring as a Promising Antibacterial Agents
title_full Molecular Docking, Synthesis, and, Biological Activity of New Diclofenac Derivatives Incorporating 1,2,4-Triazole Ring as a Promising Antibacterial Agents
title_fullStr Molecular Docking, Synthesis, and, Biological Activity of New Diclofenac Derivatives Incorporating 1,2,4-Triazole Ring as a Promising Antibacterial Agents
title_full_unstemmed Molecular Docking, Synthesis, and, Biological Activity of New Diclofenac Derivatives Incorporating 1,2,4-Triazole Ring as a Promising Antibacterial Agents
title_short Molecular Docking, Synthesis, and, Biological Activity of New Diclofenac Derivatives Incorporating 1,2,4-Triazole Ring as a Promising Antibacterial Agents
title_sort molecular docking synthesis and biological activity of new diclofenac derivatives incorporating 1 2 4 triazole ring as a promising antibacterial agents
topic Diclofenac
Molecular Docking
1,2,4-triazole
antibacterial activity
benzoyl chloride derivatives
url https://bijps.uobaghdad.edu.iq/index.php/bijps/article/view/2934
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