Antibacterial from Hypericum acmosepalum showing inhibition of ATP dependent MurE ligase from Mycobacterium tuberculosis

Abstract

In a project to characterise new antibacterial chemotypes from plants, hyperenone A and hypercalin B were isolated from the hexane and chloroform extracts of the aerial parts of H. acmosepalum. The structure of compounds were characterised by extensive 1- and 2D NMR spectroscopy and confirmed by MS spectrometry. Both hyperenone A and hypercalin B exhibited anti-bacterial activity against multidrug-resistant strains of Staphylococcus aureus, with MIC values ranging from 2–128µg/mL to 0.5–128µg/mL, respectively. Hyperenone A also showed growth inhibition against Mycobacterium tuberculosis H37Rv and M. bovis BCG at 50µg/mL (H37Rv) and 75µg/mL (BCG). The hyperenone A did not inhibit growth of Escherichia coli and was not toxic to cultured mammalian macrophages cells at the concentration at which anti-mycobacterial activity was determined. Both the compounds were also tested for their ability to inhibit MurE and MurF enzymes of M. tuberculosis which are crucial enzymes in the cytoplasmic steps of peptidoglycan biosynthesis. Hyperenone A inhibited MurE selectively whereas hypercalin B did not have any effect on both the enzymes. This is first report of a natural product from plant source showing inhibition of ATP dependent MurE ligase from M. tuberculosis. These studies represent promising starting points for further development. These highly active antibacterial compounds encourage further studies on the Hypericum genus.