Background: A dramatic increase in multiple-drug-resistant (MDR) Gram-positive pathogens has occurred in recent times, leading to increased rates or morbidity and mortality and also associated with high costs for the treatment of these infections. It is clear that there is an urgent need for the development of effective antimicrobial agents. The anti-bacterial activity of seven 2,2,6,6-tetramethylpiperidine (TMP)-substituted phenazines, compared to clofazimine (B663), were tested against 70 clinical isolates of methicillin-resistant Staphylococcus aureus, MDR Streptococcus pneumoniae and resistant Enterococcus sp.
Methods: Standard minimum inhibitory concentration agar dilution susceptibility tests were done on all isolates, including ATCC control strains.
Results: All the TMP-substituted phenazines were more active than clofazimine against all isolates tested. Compound B4125 was the most active by inhibiting all growth of the organisms tested, including vancomycin-resistant Enterococcus faecium.
Conclusion: Clofazimine has been shown to have anti-staphylococcal activity. We demonstrate enhanced anti-bacterial activity of TMP-substituted phenazines against drug-resistant Gram-positive organisms compared to clofazimine.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1159/000087454 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Antimicrobial activities of seven novel tetramethylpiperidine-substituted phenazines against multiple-drug-resistant Gram-positive bacteria.
Chemotherapy
August 2005
Department of Pharmacology, Faculty of Health Sciences, University of Pretoria, South Africa.
Background: A dramatic increase in multiple-drug-resistant (MDR) Gram-positive pathogens has occurred in recent times, leading to increased rates or morbidity and mortality and also associated with high costs for the treatment of these infections. It is clear that there is an urgent need for the development of effective antimicrobial agents. The anti-bacterial activity of seven 2,2,6,6-tetramethylpiperidine (TMP)-substituted phenazines, compared to clofazimine (B663), were tested against 70 clinical isolates of methicillin-resistant Staphylococcus aureus, MDR Streptococcus pneumoniae and resistant Enterococcus sp.
View Article and Find Full Text PDFTetramethylpiperidine-substituted phenazines inhibit the proliferation of intrinsically multidrug resistant carcinoma cell lines.
Invest New Drugs
February 2002
Department of Internal Medicine, Faculty of Medicine, University of Pretoria, South Africa.
The effects of nine new tetramethylpiperidine (TMP)-substituted phenazines on the growth of a human esophageal cancer cell line (WHCO3), two human hepatocellular carcinoma cell lines (PLC and HepG2) and three human colon cancer cell lines (CaCo2, COLO 320DM and HT29) were compared to those of clofazimine, B669 and five standard chemotherapeutic agents. The three most active TMP-substituted phenazines against these cell lines were B3962, B4126 and B4125 with mean IC50 values for all the cancer cell lines tested of 0.36, 0.
View Article and Find Full Text PDFEffects of tetramethylpiperidine (TMP)-substituted phenazines on membrane stability and P-glycoprotein function.
Int J Oncol
September 2001
Medical Research Council Unit for Inflammation and Immunity, Department of Immunology, Institute for Pathology, Faculty of Medicine, University of Pretoria, Pretoria 0001, Republic of South Africa.
The lipophilicity and membrane-destabilizing activities of clofazimine and three tetramethyl-piperidine (TMP)-substituted phenazines were compared with the anti-tumor and multiple drug resistance (MDR) neutralizing potential of these agents using a P-glycoprotein (P-gp)-expressing small cell lung cancer cell line (H69/LX4). Partition coefficients were measured as an index of lipophilicity, while membrane-destabilizing potential was measured using a conventional hemolytic assay. The membrane-destabilizing potential of the TMP-substituted phenazines was found to correlate positively with the degree of lipophilicity, as well as with MDR reversal activity.
View Article and Find Full Text PDFTetramethylpiperidine-substitution increases the antitumor activity of the riminophenazines for an acquired multidrug-resistant cell line.
Anticancer Drug Des
August 2000
Department of Immunology, Institute for Pathology, University of Pretoria, South Africa.
The multidrug resistance (MDR)-neutralizing and cytotoxic properties of five tetramethylpiperidine (TMP)-substituted phenazines were compared with those of their corresponding isopropyl-substituted analogues using a P-glycoprotein (P-gp)-expressing small cell lung cancer cell line (H69/LX4). All of the TMP-substituted phenazines tested outperformed their isopropyl analogues with respect to both cytotoxic and chemosensitizing properties, indicating the importance of TMP-substitution when designing novel riminophenazines with increased activity against MDR cancer cell lines. Of the TMP-substituted phenazines tested, B4112, chlorinated at position 3 of the phenyl- and anilino-rings, had the most potent anti-cancer activity in vitro, making this agent a potential candidate for evaluation in experimental and clinical oncology.
View Article and Find Full Text PDFAntimycobacterial action of B4128, a novel tetramethylpiperidyl-substituted phenazine.
J Antimicrob Chemother
February 2001
Medical Research Council Unit for Inflammation and Immunity, Department of Immunology, Institute for Pathology, University of Pretoria, PO Box 2034, Pretoria 0001, South Africa.
The effects of the novel tetramethylpiperidyl (TMP)-substituted phenazine, B4128 (0.6-2.5 mg/L), on growth, phospholipase A2(PLA2) activity, cation (K+, Ca2+) fluxes and energy metabolism (ATP) of Mycobacterium aurum A(+) and Mycobacterium tuberculosis (H37Ra) have been investigated in vitro.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!