Synthesis and antimicrobial activity of knipholone analogs

Abstract

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 ¹H and ¹³C 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.

Graphical Abstract

Keywords:

• Antibacterial activity
• antifungal activity
• in vitro
• knipholone
• Mannich base

Acknowledgements

ML would like to thank Addis Ababa University and University of Gondar for sponsoring his MSc study.

Disclosure statement

The authors declare no conflict of interest.

Data availability statement

Data available within the article or its supplementary materials.

Additional information

Funding

The authors reported there is no funding associated with the work featured in this article.