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Pharmaceuticals
Volume 18
Issue 2
10.3390/ph18020167
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Environmentally Friendly Synthesis of New Mono- and Bis-Pyrazole Derivatives; In Vitro Antimicrobial, Antifungal, and Antioxidant Activity; and In Silico Studies: DFT, ADMETox, and Molecular Docking

by
Oussama Merzouki
1,*,
Nadia Arrousse
2,
Elhachmia Ech-chihbi
3,
Ashwag S. Alanazi
4,
El Houssine Mabrouk
1,5,
Mohamed Hefnawy
6,
Abdelfattah El Moussaoui
7,8,
Hanane Touijer
8,
Azeddin El Barnossi
8 and
Mustapha Taleb
1
1
Laboratory of Engineering Electrochemistry, Modeling, and Environment, Department of Chemistry, Faculty of Sciences Dhar Mahraz, Sidi Mohamed Ben Abdellah University, Fez 30000, Morocco
2
School of Science and Engineering, Al Akhawayn University in Ifrane, Hassan II Avenue, Ifrane 53000, Morocco
3
Laboratory of Physics and Chemistry of Inorganic and Organic Materials, Higher Normal School, Mohammed V University, Rabat 30050, Morocco
4
Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh 11671, Saudi Arabia
5
Laboratory of Materials Engineering for the Environment and Natural Ressources, Faculty of Sciences and Technics, University of Moulay Ismail, Meknes, B.P 509, Boutalamine, Errachidia 52000, Morocco
6
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
7
Plant Biotechnology Team, Faculty of Sciences, Abdelmalek Essaadi University, Tetouan 93002, Morocco
8
Laboratory of Biotechnology, Environment, Agrifood, and Health, Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah University, Fez 30050, Morocco
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2025, 18(2), 167; https://doi.org/10.3390/ph18020167
Submission received: 30 December 2024 / Revised: 22 January 2025 / Accepted: 23 January 2025 / Published: 26 January 2025
(This article belongs to the Section Medicinal Chemistry)
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Abstract

Background/Objectives: Antimicrobial resistance and oxidative stress are major global health challenges, necessitating the development of novel therapeutic agents. Pyrazole derivatives, known for their diverse pharmacological properties, hold promise in addressing these issues. This study aimed to synthesize new mono- and bis-pyrazole derivatives using an eco-friendly, catalyst-free approach and evaluate their antioxidant, antibacterial, and antifungal activities, supported by in silico ADMET profiling, molecular docking, and Density Functional Theory (DFT) analysis. Methods: The compounds were synthesized via a green condensation reaction and characterized using NMR and mass spectrometry, which was verified by DFT analysis. Biological activities were assessed through DPPH and FRAP antioxidant assays, as well as disk diffusion and MIC methods, against bacterial strains (Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli) and fungal strains (Candida albicans and Aspergillus niger). Computational ADMET profiling evaluated pharmacokinetics and toxicity, while molecular docking assessed interactions with target proteins, including catalase, topoisomerase IV, and CYP51. Results: Theoretical calculations using DFT were in agreement with the experimental results; regarding biological activities, O4 demonstrated the most significant antioxidant activity, with 80.14% DPPH radical scavenging and an IC50 value of 40.91 µg/mL. It exhibited potent antimicrobial activity, surpassing Streptomycin with a 30 mm inhibition zone against Pseudomonas aeruginosa and showing strong efficacy against Staphylococcus aureus and Candida albicans. Computational studies confirmed favorable pharmacokinetic properties, no AMES toxicity, and strong binding affinities. DFT analysis revealed O4’s stability and reactivity, further validating its potential as a therapeutic candidate. Conclusions: This study identified and characterized novel pyrazole derivatives with promising biological and pharmacological properties. O4 emerged as the most potent compound, demonstrating strong antioxidant and antimicrobial activities alongside favorable computational profiles. These findings highlight the potential of the synthetized compounds for therapeutic development and underscore the value of integrating green synthesis with computational techniques in drug discovery.
Keywords: synthesis; pyrazole derivatives; medicinal activities; molecular docking; ADMET synthesis; pyrazole derivatives; medicinal activities; molecular docking; ADMET
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MDPI and ACS Style

Merzouki, O.; Arrousse, N.; Ech-chihbi, E.; Alanazi, A.S.; Mabrouk, E.H.; Hefnawy, M.; El Moussaoui, A.; Touijer, H.; El Barnossi, A.; Taleb, M. Environmentally Friendly Synthesis of New Mono- and Bis-Pyrazole Derivatives; In Vitro Antimicrobial, Antifungal, and Antioxidant Activity; and In Silico Studies: DFT, ADMETox, and Molecular Docking. Pharmaceuticals 2025, 18, 167. https://doi.org/10.3390/ph18020167

AMA Style

Merzouki O, Arrousse N, Ech-chihbi E, Alanazi AS, Mabrouk EH, Hefnawy M, El Moussaoui A, Touijer H, El Barnossi A, Taleb M. Environmentally Friendly Synthesis of New Mono- and Bis-Pyrazole Derivatives; In Vitro Antimicrobial, Antifungal, and Antioxidant Activity; and In Silico Studies: DFT, ADMETox, and Molecular Docking. Pharmaceuticals. 2025; 18(2):167. https://doi.org/10.3390/ph18020167

Chicago/Turabian Style

Merzouki, Oussama, Nadia Arrousse, Elhachmia Ech-chihbi, Ashwag S. Alanazi, El Houssine Mabrouk, Mohamed Hefnawy, Abdelfattah El Moussaoui, Hanane Touijer, Azeddin El Barnossi, and Mustapha Taleb. 2025. "Environmentally Friendly Synthesis of New Mono- and Bis-Pyrazole Derivatives; In Vitro Antimicrobial, Antifungal, and Antioxidant Activity; and In Silico Studies: DFT, ADMETox, and Molecular Docking" Pharmaceuticals 18, no. 2: 167. https://doi.org/10.3390/ph18020167

APA Style

Merzouki, O., Arrousse, N., Ech-chihbi, E., Alanazi, A. S., Mabrouk, E. H., Hefnawy, M., El Moussaoui, A., Touijer, H., El Barnossi, A., & Taleb, M. (2025). Environmentally Friendly Synthesis of New Mono- and Bis-Pyrazole Derivatives; In Vitro Antimicrobial, Antifungal, and Antioxidant Activity; and In Silico Studies: DFT, ADMETox, and Molecular Docking. Pharmaceuticals, 18(2), 167. https://doi.org/10.3390/ph18020167

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