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Saleem D, Ali Z H, Ibrahim N W, Abbas A K, Abd-Almonaeem T M, Al-Musawi M H et al . Exploring Pyrazole and Diazepine Derivatives: Advances in Molecular Docking, Synthesis, and Biological Activities. J Adv Med Biomed Res 2025; 33 (161) :358-371
URL: http://journal.zums.ac.ir/article-1-7853-en.html
Exploring Pyrazole and Diazepine Derivatives: Advances in Molecular Docking, Synthesis, and Biological Activities
Dina Saleem1 , Zinah Hussein Ali1 , Noor Waleed Ibrahim2 , Abbas K. Abbas3 , Toqa Monther Abd-Almonaeem1 , Mastafa H. Al-Musawi4 , Mahmoud Gharbavi *5
1- College of Pharmacy, AL-Mustansiriyah University, Baghdad, Iraq
2- Department of Pharmaceutical Chemistry, College of Pharmacy, Mustansiriyah University, Baghdad, Iraq
3- Muthanna Agriculture Directorate, Ministry of Agriculture, Al-Muthanna, Iraq
4- Department of Biology, College of Science, Mustansiriyah University, Baghdad, Iraq
5- Nanotechnology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran , gharbavi1981@gmail.com
Abstract:   (215 Views)

Background & Objective: This study focuses on the synthesis and evaluation of a series of new pyrazole and diazepine derivatives, which are significant heterocyclic compounds known for their biological and pharmacological potential. The primary objectives were to characterize the synthesized compounds, investigate their inhibitory potential against glucosamine-6-phosphate synthase via molecular docking, and evaluate their antibacterial and anticancer activities.
 Materials & Methods: The derivatives were prepared using conventional organic methods from chalcone intermediates derived from 4-aminoacetophenone, which reacted with various substituted anilines. Structural confirmation was achieved using FT-IR and 1HNMR spectroscopy. Molecular docking studies were performed to assess the binding affinities and interactions of the compounds with glucosamine-6-phosphate synthase. Biological evaluation included testing antibacterial activity against E. coli and S. aureus and assessing cytotoxicity against the MCF-7 breast cancer cell line.
Results:  Molecular docking revealed that both the pyrazole and diazepine derivatives exhibited favorable binding affinities for glucosamine-6-phosphate synthase by forming multiple stabilizing interactions within the enzyme's active site, suggesting a promising potential as enzyme inhibitors. Biological evaluation showed that some derivatives had considerable antibacterial activity, with compound 5 being especially effective against E. coli and S. aureus; its efficacy increased with concentration. Additionally, derivative 5 demonstrated notable cytotoxicity against the MCF-7 breast cancer cell line, reducing cell viability in a clear dose-dependent manner.
Conclusion:  The comprehensive study confirmed that the new pyrazole and diazepine derivatives, characterized through synthesis and spectroscopy, are promising antibacterial and anticancer leads due to favorable molecular docking profiles and demonstrated structure-activity relationships, warranting future optimization.
Keywords: Antibacterial Activity, Anticancer Agents, Chalcone Synthesis, Drug Discovery, Molecular Docking
Full-Text [PDF 1855 kb]   (20 Downloads)    
Type of Study: Original Research Article | Subject: Pharmacology
Received: 2025/09/20 | Accepted: 2025/12/7 | Published: 2025/12/12
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