Synthesis and antimicrobial activity of knipholone analogs.

In the present study, we use knipholone as a prototype molecule to identify new anti-infective agents. Since knipholone is insoluble in water, which would have a detrimental effect on its bioavailability and efficacy, we synthesized knipholone Mannich base derivatives ( 2 - 4 ) that have better predicted solubility and investigated their in vitro antimicrobial activity against eight pathogenic bacterial and fungal strains. The chemical structures of compounds 1 - 4 were elucidated from their 1 H and 13 C NMR data, and their antimicrobial activity evaluation was carried out by a broth microdilution MTT assay. Compound 3 exhibited the strongest efficacy against Staphylococcus epidermidis , with MIC value of 9.7 µg/mL. While 4 exhibited the best activity against Staphylococcus aureus , with an MIC value of 19.5 µg/mL, and was the only one to significantly inhibit the fungus Trichophyton mentagrophytes (MIC = 78.2 µg/mL). The study provides evidence for the antibacterial activity of aminoalkyl derivatives of knipholone.