Derivatives and intermediates of betulonic and platanic acid as effective antibacterial agents.

Triterpenoid acids are secondary metabolites known to possess various beneficial biological activities. Their synthetic derivatives often display improved pharmacological properties and higher levels of efficacy. In this study, we investigated, the antibacterial effects of 13 synthesized oxime derivatives and 4 intermediates of betulonic and platanic acid, comparing them with those of the unmodified forms. Six Gram-positive pathogenic human bacteria, including four resistant strains from the genus Staphylococcus, were selected for testing together with two Gram-negative bacteria. All combinations of the prepared bacterial suspensions and 17 samples (500 − 62.5 µmol/L) were placed on 96-well microtitration plates. The microdilution method was used to measure the absorbance of the samples, from which bacterial growth curves were derived. Resazurin tests were performed to obtain fluorescence values and, thereby, determine the metabolic activity and bactericidal effects. The derivatives and intermediates exhibited higher sensitivity to the Gram-positive bacteria. The most effective samples, for which 90–100% growth inhibition was observed against resistant strains (S. aureus 368, S. epidermidis 335), were the oxime ester derivative of betulonic acid synthesized from 1-adamantylacetic acid (14; 500 µmol/L) and the C-3 acetate intermediate of platanic acid (18; 500 µmol/L). Sample 18 also showed 90–100% inhibition against S. aureus 670. Thus, our results suggest that the tested triterpenoid derivatives and intermediates have considerable potential for the development of new antibiotic therapies.