Tabebuia avellanedae naphtoquinones: Activity against methicillin-resistant staphylococcal strains, cytotoxic activity and in vivo dermal irritability analysis

Abstract

Background: Methicillin-resistant Staphylococcus aureus (MRSA) and coagulase-negative staphylococcus infections are a worlwide concern. Currently, these isolates have also shown resistance to vancomycin, the last therapy used in these cases. It has been observed that quinones and other related compounds exhibit antibacterial activity. This study evaluated the antibacterial activity, toxicity and in vivo dermal irritability of lapachol extracted from Tabebuia avellonedae and derivatives against methicillin-resistant staphylococcal isolates. In addition, its mechanism of action was also analyzed. Methods: The compounds β-lapachone, 3-hydroxy β N lapachone and α-lapachone were tested to determine the MIC values against methicillin-resistant S. aureus, S. epidermidis and S. haemolyticus strains, being the two last ones heteroresistant to vancomycin. Experiments of protein synthesis analysis to investigate the naphthoquinones action were assessed. In vitro toxicity to eukaryotic BSC-40 African Green Monkey Kidney cell cultures and in vivo primary dermal irritability in healthy rabbits were also performed. Results: The compounds tested showed antibacterial activity (MICs of 8, 4/8 and 64/128 [μg/mL to β-lapachone, 3-hydroxy β N lapachone and α-lapachone, respectively), but no bactericidal activity was observed (MBC > 512 μg/ml for all compounds). Although it has been observed toxic effect in eukaryotic cells, the compounds were shown to be atoxic when applied as topic preparations in healthy rabbits. No inhibition of proteins synthesis was observed. Conclusion: Our results suggest that quinones could be used in topic preparations against wound infections caused by staphylococci, after major investigation of the pharmacological properties of the compounds. Studies about the use of these compounds on tumoral cells could be carried on, due to their effect in eukaryotic cells metabolism. © 2006 Pereira et al; licensee BioMed Central Ltd.