Specific Gram-Positive Antibacterial Activity of 4-hydroxy-3-(3-methyl-2-butenyl) Acetophenone Isolated from Senecio graveolens

Background: Resistance to antimicrobial drugs has become an increasingly global problem, and is the main reason for an extended search for new drugs to treat microbial infections. Senecioneae is one of the largest tribes of Asteraceae, comprised of about 150 genera and 3000 plant species. Senecio graveolens, commonly called Chachacoma, is highly used as a medicinal plant for altitude sickness by the natives of the Andes Mountains around the Atacama Desert. Previous studies have demonstrated that S. graveolens extracts possess antibacterial properties, but its active compound and molecular mechanisms are still unknown.
Methods: Form the ethanolic extract of S. graveolens the main compound 4-hydroxy-3-(3-methyl-2-butenyl)acetophenone (4-H-3-(MB)AP) was identify and purified by nuclear magnetic resonance (NMR). Antibacterial activity of (4-H-3-(MB)AP) was assayed on Gram-positive and Gram-negative bacteria by microbiological techniques. Possible mechanisms of action of (4-H-3-(MB)AP) were explored by microbiological, flow cytometry and electron microscopy techniques.
Results: Here we determined that S. graveolens extract has specific antibacterial activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus, and Mycobacterium smegmatis. The most abundant compound from S. graveolens extract, 4-H-3-(MB)AP, showed broad antibacterial activity against Gram-positive but no activity against Gram-negative strains. We determined that 4-H-3-(MB)AP permeabilizes bacterial membranes and precludes cell division by disrupting Gram-positive bacteria divisome, suggesting that the synthesis of teichoic acid is inhibited.
Conclusions: We conclude that 4-H-3-(MB)AP is one of the active compounds of S. graveolens extract responsible for its antibacterial activity. 4-H-3-(MB)AP is a candidate for further chemical modification studies and practical approaches to design antimicrobial drugs.