N-(2-trifluoromethyl-4-chlorophenyl)-2-oxocyclohexyl sulfonamide (chesulfamide) is in the limelight as a novel fungicide, and has fungicidal activity against Botrytis cinerea. For exploring more novel structures, 33 new compounds were synthesized by N-alkylation and acid–amine coupling reactions with chesulfamide as the core moiety, and their structures were characterized and established by ¹H-NMR, ¹³C-NMR, MS, and elemental analysis. The structure of (1R,2S)-2-(2-(N-(4-chloro-2-trifluoromethylphenyl)sulfamoyl)-cyclohexylamino)-N-(2-trifluoromethylphenyl) acetamide (II-19) was defined by X-ray single crystal diffraction. The in vivo and in vitro fungicidal activities against B. cinerea were evaluated. The bioassay results of mycelial growth demonstrated that most compounds exhibited excellent inhibitory activity against B. cinerea at 50 μg mL⁻¹, and 7 compounds showed lower EC₅₀ values than boscalid (EC₅₀ = 4.46 μg mL⁻¹) against B. cinerea (CY-09). In cucumber pot experiment, the inhibitory rates of four compounds (II-4, II-5, II-12, and II-13) against B. cinerea were 90.48, 93.45, 92.86, and 91.07, which were better than cyprodinil (88.69%), the best performing of all controls. In tomato pot experiment, the control efficacy of two analogs (II-8 and II-15) were 87.98 and 87.97% at 200 μg mL⁻¹, which were significantly higher than boscalid (78.10%). Most compounds have an excellent fungicidal effect on B. cinerea, with potential as a lead compound for developing new pesticides.

To address the urgent challenge of antimicrobial resistance, a series of twenty novel C-28 modified betulinic acid derivatives was designed and synthesized. Several derivatives, particularly 3b, 3d, 3e, and 3o, displayed notable antibacterial activity against Gram-positive bacteria, including Staphylococcus aureus and vancomycin-resistant Staphylococcus aureus (VRSA). The most active compound, 3d, was subjected to further mechanistic evaluation: it produced concentration-dependent inhibition zones in Oxford cup assays, exhibited bactericidal kinetics in time-kill studies, and significantly suppressed biofilm formation. Molecular docking suggested that the anti-biofilm activity of 3d may be mediated through binding to the staphylococcal accessory regulator A (SarA), a key transcriptional regulator of biofilm formation. The molecular dynamics study provided additional confirmation of the effective binding between 3d and SarA. These results highlight compound 3d as a promising lead for the development of novel anti-biofilm agents targeting drug-resistant Gram-positive infections.

The escalating crisis of bacterial antimicrobial resistance necessitates the discovery of novel antibacterial agents with distinct mechanisms of action. Ursolic acid (UA), a naturally abundant pentacyclic triterpenoid, serves as a promising scaffold for structural modification. In this study, a series of 26 novel UA derivatives (A1–A7 and B1–B19) were designed and synthesized by introducing various substituents at the C-28 carboxyl group via a chloroacetyl chloride linker. Their antibacterial activities were evaluated against S. aureus, S. epidermidis, E. coli, and P. aeruginosa using the microbroth dilution method. Among them, compound B1 exhibited the most potent activity, with a minimum inhibitory concentration (MIC) of 37.5 μg/mL against S. aureus and 75 μg/mL against E. coli. Antibacterial kinetic and time-kill curve assays confirmed the sustained bactericidal effect of B1. Furthermore, B1 significantly inhibited biofilm formation in both S. aureus and E. coli in a time-dependent manner. Molecular docking studies revealed that B1 binds spontaneously to the S. aureus SarA protein through three hydrogen bonds and π-π stacking interactions, providing a structural basis for its antibacterial and anti-biofilm activities. This study demonstrates that piperazine-modified UA derivative B1 is a promising antibacterial candidate and offers a new strategy for the structural optimization of ursolic acid.