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

Abstract

BackgroundMethicillin-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.MethodsThe 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 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.ResultsThe 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.ConclusionOur 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.

Performance of chromogenic media for Candida in rapid presumptive identification of Candida species from clinical materials

“…Although C. dubliniensis colonies are dark green unlike light green colonies of C. albicans , this difference may be inadequate for primary identification and often lost after serial subculture. [2324] Hospenthal et al reported all C. dubliniensis strains ( n = 17) in their study had colonies identical to C. albicans on CAC. In this study, we isolated one C. dubliniensis, which had typical dark green colonies.…”

Anti-infectious activity in plants of the genus Tabebuia

“…It was found that the (-)-5-hydroxy-2-(1'-hydoxyethyl) naphtho [2,3-b]furan-4,9-dione (3) and its positional isomer (-)-8-hydroxy-2-(1'-hydoxyethyl) naphtho [2,3-b]furan-4,9-dione (4) had a strong activity against Staphylococcus aureus and Bacillus subtilis, with MICs varying between 0.78 and 6.25 µg/mL (0.78 and 6.25 mg/L) (Yamashita et al 2009); these naphthoquinones are found in the inner bark of Tabebuia avellanedae (Wagner et al 1989). Other naphthoquinone derivatives obtained from the Tabebuia avellanedae-isolated lapachol (5), such as β-lapachone (6) and (±) 3-hydroxy-β-Nlapachone (7), displayed a considerable inhibitory activity against Staphylococcus aureus growth, with MICs of 8 µg/mL (8 mg/L) for both compounds; however, no bactericidal activity was observed (Minimum Bactericidal Concentration, MBC≥512 µg/mL (512 mg/L) (Pereira et al 2006). Lapachol, which is a biologically active naphthoquinone showed activity against several agents such as bacteria, fungus, viruses and parasites and has therefore been used as a target for the synthesis of naphthoquinone derivatives with potent antimicrobial activity (Hussain et al 2007).…”

Reduction of doxorubicin-induced genotoxicity by Handroanthus impetiginosus in mouse bone marrow revealed by micronucleus assay

“…The expression of NQO1 in solid cancers is higher than in normal tissues (Belinsky and Jaiswal., 1993), including in carcinoma of the liver (Schlager and Powis, 1990), colon (Smitskamp-Wilms et al, 1995), breast (Schlager and Powis, 1990;Smitskamp-Wilms et al, 1995), brain (Berger et al, 1985), and lung (Schlager and Powis, 1990). In addition, NQO1 has been shown to be an important factor in β-lapachone-induced cell death in many kinds of cancer cells (Pink et al, 2000;Reinicke et al, 2005), including breast cancer (Tagliarino et al, 2003), glioma (Park et al, 2011), and prostate cancer (Pink et al, 2000). In this context, other methods have been examined to increase NQO1 expression or activity in cancer cells (Terai et al, 2009;Tan et al, 2012;Satsu et al, 2012) in order to increase the clinical efficacy of β-lapachone.…”

“…The anticancer activity of β-lapachone may involve its catalysis by NAD(P) H:quinone oxidoreductase (NQO1, DT-diaphorase), which used NAD(P)H or NADH as an electron source to yield the two-electron reduction of β-lapachone (Pardee et al, 2002;Reinicke et al, 2005). In the presence of NQO1, β-lapachone underwent reduction to an unstable hydroquinone, resulting in the generation of ROS, including superoxides (Pink et al, 2000;De Witte et al, 2004;Choi et al, 2007). In turn, these reactive oxygen species oxidized thiol groups of the mitochondrial potential transition pore complex, leading to increased inner membrane permeability, reduced membrane depolarization, release of cytochrome c, and cell death (Lemasters et al, 1998;Smaili et al, 2000).…”