Pyrene‐linked heterocyclic pyrazoles: Synthesis, antimicrobial screening, and in silico molecular insights

Abstract

Abstract A library of structurally diverse pyrene‐linked pyrazole derivatives was designed and synthesized, and their antimicrobial properties along with molecular interaction behavior were systematically investigated. The target compounds were efficiently prepared through a straightforward synthetic approach and fully characterized using standard spectroscopic techniques, confirming the formation of the desired heterocyclic framework. Biological evaluation against selected Gram‐positive, Gram‐negative, and fungal strains showed noticeable differences in activity across the series, indicating a strong dependence on the nature and position of substituents as well as their electronic characteristics. Notably, compound 4h emerged as the most active derivative, exhibiting significant antibacterial effects with inhibition zones of approximately 38 mm against Staphylococcus aureus and 29 mm against Proteus vulgaris, demonstrating broad‐spectrum potential. To better understand these results, molecular docking studies were carried out against the Escherichia coli FabB enzyme. Compound 4 h showed the most favorable binding energy (ΔG = −8.9 kcal/mol), supported by stable hydrogen bonding and hydrophobic interactions within the enzyme's active site. In silico analysis also revealed a cLogP value of 7.3390, indicating suitable lipophilicity consistent with drug‐like behavior. In summary, the integration of experimental antimicrobial assessment with computational studies supports the pyrene–pyrazole framework as a promising scaffold for the further development of effective antimicrobial agents.