Synergistic effect of the antibacterial compound 23-methyl-6-O-desmethylauricepyrone isolated from Achyrocline satureioides.

JORAY M.B.; PALACIOS S. M.; CARPINELLA M.C.

AAPS PHARMSCITECH

SPRINGER

Año: 2011 vol. 12 p. 795 - 796

1530-9932

Staphylococcus aureus causes a wide range of infectious diseases in humans (1) from relatively mild skin infections such as folliculitis and furunculosis to life-threatening conditions, including sepsis, deep abscesses, pneumonia, osteomyelitis, and infective endocarditis (2). As a result of a study of the antibacterial activity of Achyrocline satureioides a bioactive compound was identified. A remarkable inhibitory effect of this compound on the mentioned pathogenic bacterium was determined. Then, the antibacterial activity of combinations of this active principle with subinhibitory concentrations of commercial antibiotics was investigated. Materials and methods The structural elucidation of the isolated compound was achieved through different spectroscopic techniques. The MIC, MBC and synergistic studies were carried out by micro dilution test in agar according to CLSI (3) against Staphylococcus aureus (ATCC 6538) used as reference. Results The most active compound present in A. satureioides extract was identified as 23-methyl-6-O-desmethylauricepyrone (1). Despite 23-methyl-6-O-desmethylauricepyrone has already been described in A. satureioides (4), this is the first time that any biological activity has been attributed to it. The compound demonstrated a strong antibacterial activity against S. aureus with MIC and MBC values of 2 and 8 µg/mL, respectively. These results are very encouraging; this active principle exceeded the activity shown by the commercial agents used as reference. The activity of 23-methyl-6-O-desmethylauricepyrone is comparable to that of other commercial antibiotics like vancomycin (MIC = 0.5-2 µg/mL) or chloranphenicol (MIC = 2-8 µg/mL) (5). When the compound was combined at 1/2 MIC (1 µg/mL) with erythromycin and gentamicin, bacterial growth was still inhibited even when the concentration of the two last was 256 and 128 times under their MIC value, respectively. Even at 16 times below its MIC, compound 1 exhibited antibacterial activity in combination with erythromycin at 16 times below its MIC. According to the obtained results, compound 1 could arise as a new antibacterial agent against staphylococcal infections, not only because of its effectiveness but also because of the synergistic effect with conventional antibiotics. These facts take relevance considering that most of the antibacterial agents used today have many side effects (6). Therefore, reducing their doses could contribute to a healthier lifestyle. References 1. Kanafani ZA, Fowler Jr. VG. Enferm Infecc Microbiol Clin. 2006; 24 (3) 182-193. 2. Lowy FD. N. Engl. J. Med. 1998; 339, 520?532. 3. Clinical and Laboratory Standards Institute, 2006. 7th ed. Approved Standard M7-A7. 4. Hirschmann GS. Rev. Latinoamer Quim. 1984; 15: 134-135. 5. National Committee for Clinical Laboratory Standards, 1998.Vol. 18, N° 1. 6. Kocak Z, Hatipoglu CA, Ertem G, Kinikli S, Tufan A, Irmak H et al. J Infect. 2006; 52: 49-52.