Synthesis, antimicrobial evaluation, and molecular docking of novel pyrene-functionalized pyrazole derivatives

• Novel polynuclear pyrene-based pyrazoles were efficiently designed and synthesized. • Structures were confirmed by NMR and mass spectrometric analyses. • Pyrazoles showed broad-spectrum antibacterial and antifungal activity. • Pyrazole 4 g exhibited low MIC values comparable to standard drugs. • Molecular docking and SAR studies supported experimental antimicrobial results. The rising challenge of antimicrobial resistance creates an urgent need for new antimicrobial agents. In this study, a series of polynuclear pyrene-based pyrazole derivatives was designed and synthesized using an efficient synthetic method. The structures of the synthesized compounds were confirmed by standard spectroscopic techniques, including NMR and mass spectrometry. The antimicrobial activity of these compounds was evaluated in vitro against selected Gram-positive and Gram-negative bacterial strains, and their potency was determined using minimum inhibitory concentration (MIC) values. Pyrazole 4g displayed promising antibacterial and antifungal activity against S. aureus , producing an inhibition zone of about 35mm and against A. flavus , with an inhibition zone of 41mm respectively. Among the tested compounds, pyrazole 4g showed the most promising antibacterial and antifungal activity, with low MIC values of 8.0µg/mL against Staphylococcus aureus and 14.0 µg/mL against Aspergillus flavus , comparable to standard drugs. Molecular docking studies supported the experimental results (ΔG = –9.2 kcal/mol) by revealing stable binding modes and key hydrogen-bond and hydrophobic interactions within bacterial target enzymes. Structure–activity relationship analysis highlighted the importance of the pyrazole core and suitable heterocyclic substitution for enhanced antimicrobial activity. Overall, these findings suggest that heterocyclic biphenyl-based pyrazoles are promising lead compounds for further antimicrobial development.