Design, synthesis and characterization of new fused pyrazole systems: In Vitro anti-bacterial, anti-fungal, antioxidant evaluation, In Silico DFT and molecular docking studies Wesam S. Shehab a , Naja Magdy b , Muhammed A.R. Elhoseni a , Mohamed G. Assy a , Mohamed H.M. AbdEl-Azim a , Abdulrahman E. Mesbah c , Walaa H. El-Shwiniy d,* , Mostafa M.K. Amer e,f , Doaa A. Elsayed a a Department of Chemistry, Faculty of Science, Zagazig University, Zagazig, 44519, Egypt b Al-Farahidi University, Baghdad, Iraq c Department of Chemistry, Faculty of Science, Mansoura University, Mansoura, 35516, Egypt d Department of Chemistry, College of Science, University of Bisha, Bisha 61922, Saudi Arabia e Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China f University of Chinese Academy of Sciences, Beijing, China A R T I C L E INFO Keywords: Furopyrazole Pyrazolopyran, β- diketone Polyheterocyclic Dipyrazolopyran Pyrazolopyridine ABSTRACT This research investigates the synthesis, characterization, and biological assessment of new heterocyclic de- rivatives generated from pyrazole frameworks, with the goal of determining their antibacterial and antioxidant capabilities. Numerous processes, including as cyclocondensation, oxidative cyclization, and functional group transformations, are used in the synthetic approach to produce a variety of derivatives with distinctive structural characteristics. Important compounds like furopyrazole (6) shown strong antioxidant capacity (87.6 % ABTS inhibition), almost matching ascorbic acid, and remarkable antifungal activity against Candida albicans (15.6 mm/mg) and Aspergillus flavus (7.8 mm/mg). Compound 8 showed balanced performance because of its nitrile functionality, but compound 9 showed strong antibacterial and antioxidant activities. Functional groups like thiourea, nitrile, and aromatic rings are essential for boosting biological activity, according to structure-activity relationship (SAR) studies. Thiourea, in particular, emerged as a pivotal moiety, contributing to radical stabi- lization and improved microbial interactions. The findings emphasize the potential of these derivatives for therapeutic applications, with compound 6 emerging as a promising candidate for antifungal and antioxidant use. Furthermore, Computational chemistry studies density functional studies along with molecular docking were performed using the cytochrome c peroxidase enzyme with ascorbic acid as reference ligand. 1. Introduction Heterocycles of nitrogen are a basic type of chemicals that are found in many physiologically active substances. Among them, pyrazole is a nitrogen-containing heterocycle with five members that is distinguished by having two nearby nitrogen atoms in its ring structure. Its varied pharmacological characteristics are mostly due to this structural char- acteristic. Numerous biological actions, such as anticancer [1,2](Crizo- tinib II [3], Pyrazofurin IV [4]), anti-inflammatory (celecoxib I) [5], antioxidant [6], antibacterial [7], antiviral [8], antifungal [9], anti- emetic [10], anticoagulant (Apixaban III) [11] and antidepressant (Fezolamine V) [12] properties, have been shown for pyrazole and its derivatives [13–19], Fig. 1. Because of these characteristics, pyrazole has become an essential scaffold in medicinal chemistry, and many research have been conducted to examine its potential in drug discovery and design. The fact that pyrazole is included in several commercially accessible medications serves as more evidence of its importance in medicines [20–22]. As the first positive allosteric modulator of the human metabotropic glutamate receptor, CDPPB, for example, may be useful as a treatment for neurological conditions. Likewise, rheumatoid arthritis and other inflammatory diseases are commonly treated with celecoxib, a * Corresponding author. E-mail address: whelmy@ub.edu.sa (W.H. El-Shwiniy). Contents lists available at ScienceDirect Journal of Molecular Structure journal homepage: www.elsevier.com/locate/molstr https://doi.org/10.1016/j.molstruc.2025.142163 Received 11 December 2024; Received in revised form 6 March 2025; Accepted 23 March 2025 Journal of Molecular Structure 1337 (2025) 142163 Available online 25 March 2025 0022-2860/© 2025 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.