2. Academic Validation
  3. Synthesis, X-Ray Structure, Characterization, Antifungal Activity, DFT, and Molecular Simulation of a Novel Pyrazole Carboxylic Acid

Synthesis, X-Ray Structure, Characterization, Antifungal Activity, DFT, and Molecular Simulation of a Novel Pyrazole Carboxylic Acid

  • Curr Top Med Chem. 2025 Jan 21. doi: 10.2174/0115680266348692241211111312.
Said Tighadouini 1,  Imane Yamari 2,  Othmane Roby 1,  Abdullah Y A Alzahrani 3,  Oussama Abchir 2,  Imane Nait Irahal 4,  Rafik Saddik 1,  Marilena Ferbinteanu 5,  Samir Chtita 2
Affiliations

Affiliations

  • 1 Laboratory of Organic Synthesis, Extraction, and Valorization, Faculty of Sciences Ain Chock, Hassan II University, Route d'El Jadida Km 2, Casablanca BP 5366, Morocco.
  • 2 Laboratory of Analytical and Molecular Chemistry, Faculty of Sciences Ben M'Sik, Hassan II University of Casablanca, B. P 7955 Casablanca, Morocco.
  • 3 Department of Chemistry, Faculty of Science and Arts, King Khalid University, Mohail Assir, Saudi Arabia.
  • 4 Health and Environment Laboratory, Faculty of Sciences Ain Chock, Hassan II University, Route d'El Jadida Km 2, Casablanca BP 5366, Morocco.
  • 5 Inorganic Chemistry Department, Faculty of Chemistry, University of Bucharest, Bucharest 050663, Romania.
PMID: 39844551 DOI: 10.2174/0115680266348692241211111312
Abstract

Background: The search for new Antifungal agents is critical due to the rising resistance of Fungal pathogens to existing treatments. This study focuses on the synthesis and evaluation of a novel compound, 1-benzyl-5-methyl-1H-pyrazole-3-carboxylic acid (compound L1), as a potential Antifungal agent.

Methods: Compound L1 was synthesized and characterized using a range of analytical techniques, including 1H^1H1H NMR, 13C^{13}C13C NMR, FT-IR, GC-MS, and X-ray single crystal diffraction (XRD). The Antifungal activity of the compound was assessed in vitro, and its molecular structure was studied using Density Functional Theory (DFT). Molecular docking and dynamics simulations were conducted to evaluate the interaction of the compound with sterol 14-alpha demethylase (CYP51) from Candida albicans. ADME/Tox evaluations were also performed to assess the drug-like properties of compound L1.

Results: Compound L1 exhibited moderate Antifungal activity with an IC50 value of 34.25 μg/mL. DFT studies confirmed the highly stable molecular structure of the compound. Molecular docking and dynamics simulations demonstrated that compound L1 had a higher affinity and stability when forming complexes with the crystal structure of CYP51, particularly in interaction with the tetrazole- based Antifungal drug candidate VT1161 (PDB ID: 5TZ1). ADME/Tox evaluations indicated favorable drug-like properties for compound L1.

Conclusion: The results suggest that compound L1 is a promising Antifungal candidate, showing greater potential than fluconazole in the conducted evaluations. Further studies are warranted to explore its full therapeutic potential.

Keywords

ADMETox profile; Density Functional Theory calculation; Pyrazole carboxylic acid; antifungal activity; dynamic simulation.; molecular docking.

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