MOLECULAR DOCKING, ADMET, SYNTHESIS, AND PRELIMINARY PHARMACOLOGICAL EVALUATION OF NEW ETODOLAC DERIVATIVES CONTAINING PYRAZOLINE MOIETY
DOI:
https://doi.org/10.22159/ajpcr.2025v18i11.56550Keywords:
Molecular Docking, Anti-inflammatory, Antimicrobial activity, Etodolac hydrazide, PyrazolineAbstract
Objective: The main objectives were to use molecular docking to create compounds with antibacterial activity and anti-inflammatory properties that are still effective. For future application, these compounds must also have acceptable absorption, distribution, metabolism, excretion, and possible toxicity (ADMET) characteristics.
Methods: Ligand Designer using Glide (Schrodinger LLC) molecular docking studies. A new etodolac derivative containing a pyrazoline ring was synthesized and characterized using ATR-FTIR and 1H-NMR. Furthermore, their pharmacological activities were investigated. In order to determine the derivatives’ pharmacological characteristics, we used a rat model for anti-inflammatory activity called rat egg white-induced paw edema. The agar-well diffusion method was used to assess the in vitro antimicrobial activity of the test substances against a variety of microorganisms.
Results: The newly synthesized compounds HF7 and HF9, as shown in the molecular docking study findings with the cyclooxygenase-2 protein (PDB code: 4m11), exhibit binding energies of −9.247 and −8.716, respectively, which are greater than the reference docking result. During docking analysis using the Saccharomyces cerevisiae CYP51 receptor (PDB code: 4wmz), all synthesized compounds demonstrated higher docking scores compared to fluconazole, which served as the reference standard. The rat paw edema technique showed considerable action of HF6 and HF8 have a stronger impact compared to the standard impact. According to antimicrobial research results, HF8’s (minimum inhibitory concentration [MIC]) against Staphylococcus aureus and Streptococcus pyogenes is 64 mcg/mL, whereas derivatives HF7 and HF11 also demonstrated MIC of 64 mcg/mL against S. aureus.
Conclusion: The effective synthesis of a new class of pyrazoline compounds was achieved. Most of the recently identified pyrazoline compounds were more effective against the microorganisms under investigation, with compounds HF7, HF8, and HF11 showing the greatest effectiveness in comparison to the standards used (fluconazole and amoxicillin).
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