title: Antibacterial activity of the plant-derived compounds 23-methyl-6-O-desmethylauricepyrone and (Z,Z)-5-(trideca-4,7-dienyl)resorcinol and their synergy with antibiotics against methicillin-susceptible and -resistant Staphylococcus aureus.
abstract: The present study investigated the antibacterial activity of two plant-derived compounds, 23-methyl-6-O-desmethylauricepyrone (1) and (Z,Z)-5-(trideca-4,7-dienyl)resorcinol (2), and their synergistic effects with erythromycin and gentamicin against methicillin-susceptible (MSSA) and gentamicin- and methicillin-resistant Staphylococcus aureus (MRSA). Studies of the individual antibacterial activity of each plant-derived compound and synergy experiments were carried out, by the microdilution test in agar and by the checkerboard method, respectively. Compound 1 showed minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 2 and 8 μg/mL, respectively, against both strains of S. aureus, while compound 2 exhibited anti-MSSA and anti-MRSA activity with MICs and MBCs of 4 and 8 and 2 and 8 μg/mL, respectively. Time-kill curves showed that, while compound 1 produced complete killing of both strains at 24 h from the beginning of the experiment, 2 produced the same effect in the first hour. Combinations of 1 with erythromycin or gentamicin showed a notable synergism against MSSA, which enabled the antibiotic concentration to decrease by up to 300 or 260 times, respectively. When the aminoglycoside was placed together with compound 2, only an additive effect was observed. The assayed compounds did not produce erythrocyte hemolysis or genotoxicity and they did not affect macrophage viability at the effective or higher concentrations. These results suggest that both compounds could be considered as promising antibacterial agents while compound 1 could be used in combinatory therapies with erythromycin and gentamicin.
authors.affiliation: Fine Chemicals and Natural Products Laboratory, School of Chemistry, Catholic University of Córdoba, Camino a Alta Gracia Km 10 (5000), Córdoba, Argentina.
authors.forename: Mariana B
authors.initials: MB
authors.lastname: Joray
authors.forename: María L
authors.initials: ML
authors.lastname: González
authors.forename: Sara M
authors.initials: SM
authors.lastname: Palacios
authors.forename: María C
authors.initials: MC
authors.lastname: Carpinella
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004357:Drug Synergism; D004912:Erythrocytes / Q000187:drug effects; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D010936:Plant Extracts / Q000494:pharmacology*; D010944:Plants / Q000737:chemistry*; D011753:Pyrones / Q000494:pharmacology*; D012118:Resorcinols / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects*
chemical_list: C568787:(Z,Z)-5-(trideca-4,7-dienyl)resorcinol; C452206:23-methyl-6-O-desmethylauricepyrone; D000900:Anti-Bacterial Agents; D010936:Plant Extracts; D011753:Pyrones; D012118:Resorcinols