Rapid synthesis and antifungal evaluation of prenylated chalcones: A structure-activity relationship and molecular docking study

• Rapid synthesis of prenylated chalcones by microwave method. • Promising antifungal activities against Scloretium rolfsii and Fusarium oxysporum confirmed by antifungal bioassay. • Molecular docking studies suggested favorable interactions and strong binding energies within the target sites. • SAR and QSAR studies revealed the key structural elements responsible for bioactivity. Microwave-assisted green synthesis was employed to synthesize a series of prenylated chalcones, resulting from the reaction of 4-prenyloxy-2-hydroxy-acetophenone with diverse benzaldehydes. A comparative analysis of reaction times and yields revealed significant advantages of the microwave method, with reaction times ranging from 1 to 3.2 min, compared to 12 to 48 hrs using conventional methods. The structural elucidation of the synthesized compounds was achieved through a combination of spectroscopic techniques, including IR, 1 H NMR, 13 C NMR and LC-HRMS. In vitro antifungal assays were performed against Sclerotium rolfsii and Fusarium oxysporum to evaluate the efficacy of these compounds, which was further supported by Structure-activity Relationships (SAR) and molecular docking studies. The most effective compound against S. rolfsii , was found to be 2′-Hydroxy-4-bromo-4′- O -prenylchalcone ( 5E ) with ED 50 = 23.28 mg L −1 , while 2′-Hydroxy-2,6-dichloro-4′- O -prenylchalcone ( 5B ) (ED 50 = 25.70 mg L −1 ) exhibited the highest activity against F. oxysporum . The molecular docking study was done for targeting two different fungi, namely, S. rolfsii ( DNA directed RNA polymerase : RPB2 gene target) and F. oxysporum ( Cutinase: FoCut5a target gene). Docking results showed that the docked molecules exhibited binding energies ranging from −31.0476 to −19.3568 kcal/mol for S. rolfsii and from −38.9474 to −26.5031 kcal/mol for F. oxysporum , highlighting the potential of these compounds as effective inhibitors. Furthermore, additional docking metrics, indicated stable interactions.