Tabebuia avellanedae naphthoquinones: activity against methicillin-resistant staphylococcal strains, cytotoxic activity and in vivo dermal irritability analysis.
BACKGROUND
Methicillin-resistant Staphylococcus aureus (MRSA) and coagulase-negative staphylococcus infections are a worldwide 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 avellanedae and derivatives against methicillin-resistant staphylococcal isolates. In addition, its mechanism of action was also analyzed.


METHODS
The compounds beta-lapachone, 3-hydroxy beta N lapachone and alpha-lapachone were tested to determine the MIC values against methicillin-resistant S. aureus, S. epidermidis and S. haemolyticus strains, being the two last ones hetero-resistant 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 microg/mL to beta-lapachone, 3-hydroxy beta N lapachone and alpha-lapachone, respectively), but no bactericidal activity was observed (MBC > 512 microg/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.


CONCLUSIONS
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.
Pereira
Eliezer Menezes
EM
Instituto de Microbiologia Prof, Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. pereiraem@ufrj.br
Machado
Thelma de Barros
Tde B
Leal
Ivana Correa Ramos
IC
Jesus
Desyreé Murta
DM
Damaso
Clarissa Rosa de Almeida
CR
Pinto
Antonio Ventura
AV
Giambiagi-deMarval
Marcia
M
Kuster
Ricardo Machado
RM
Santos
Kátia Regina Netto dos
KR
D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D007509:Irritants / Q000633:toxicity*; D016106:Methicillin Resistance; D009285:Naphthoquinones / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D011817:Rabbits; D012867:Skin / Q000187:drug effects / Q000473:pathology*; D013211:Staphylococcus aureus / Q000187:drug effects*; D013212:Staphylococcus epidermidis / Q000187:drug effects*; D041162:Staphylococcus haemolyticus / Q000187:drug effects*; D029663:Tabebuia / Q000737:chemistry*
D007509:Irritants; D009285:Naphthoquinones; D010936:Plant Extracts