Sensitivity of Trichomonas vaginalis to metronidazole, tinidazole, and nifuratel in vitro.
Prompted by the sensitivity of trichomonads to metronidazole and nifuratel in clinical practice, a study was conducted in 1971-1972 of 63 consecutive strains of Trichomonas vaginalis isolated from women with clinically refractory vaginal discharge. Their susceptibility to metronidazole, tinidazole, and nifuratel was tested, using a serial tube dilution technique. The minimum concentrations which in 48 hrs caused immobilization and lysis of trichomonads cultured in Diamond's medium was assessed. No differences in drug potency could be determined. The median trichomonistatic and trichomonicidal concentrations were 0-1 and 0-6 mug/ml. respectively when using an inoculum of 10,000 organisms per ml. An inoculum of 100,000 per ml. resulted in inhibitory concentrations of 1-0 and killing concentrations of 3-3 mug./ml. These levels are readily attained in blood and vaginal tissue after oral ingestion of the two imidazole derivatives. Thus, metronidazole has maintained its efficacy since it was first introduced more than a decade ago. The few therapeutic failures with metronidazole and tinidazole are considered to have been caused by pharmacokinetic deficiencies in the patients, or by re-infection. (+info)
Mutagenicity of nitrofurans, nitrothiophenes, nitropyrroles, nitroimidazole, aminothiophenes, and aminothiazoles in Salmonella typhimurium.
Thirty-two heterocyclic compounds, including 24 nitroheterocycles, 7 aminoheterocycles and derivatives, and 1 thiophene lacking a nitro group, were tested for mutagenic activity in Salmonella typhimurium TA 98 and TA 100. All the nitroheterocycles (11 new), including nitrofurans, nitrothiophenes, nitropyrroles, and 1 nitroimidazole, were mutagenic in TA 100; 13 were also mutagenic in TA 98. 5-Nitro-2-furoic acid, a noncarcinogen, was mutagenic in TA 100. Seven carcinogenic nitroheterocycles were mutagenic in both strains. Seven aminoheterocycles (4 new), aminothiophenes and aminothiazole derivatives, and 1 thiophene without a nitro group were not mutagenic. Both TA 98 and TA 100 were uvrB and lacked the ability of excision repair of DNA. Among the 24 mutagenic nitroheterocycles, only 13 compounds exhibited bacterial killing effects, suggesting that more than 1 mechanism may be involved in the interaction of nitroheterocycles with bacterial DNA. (+info)
Bactericidal activity of nitrofurans against growing and dormant Mycobacterium bovis BCG.
Depletion of oxygen triggers the shift-down of Mycobacterium bovis BCG to a state of dormancy. Bacilli in their dormant state are resistant to standard anti-mycobacterials. The nitroimidazole metronidazole was the first compound identified to show bactericidal activity against dormant tubercle bacilli. In contrast to metronidazole's selective toxicity for dormant bacilli, we report here that the nitrofurans nitrofurantoin, furaltadone and nitrofurazone showed bactericidal activity against dormant and growing bacteria. Importantly, the bactericidal effect of nitrofurans on dormant bacilli was 35- to 250-fold higher compared with metronidazole. (+info)
Statistical analysis on toxicity of a nitrofuran derivative, 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide.
A food additive, furylfuramide or AF-2, which had been used in Japan since 1965 and structurally is composed of 5-nitro-2-furyl radical and acrylamide, was re-examined mainly on chronic toxicity by statistically reviewing published data. The conclusions are as follows: 1) The maximum safety dosage which shows no demonstrable change in rats must be corrected at least to 1/170 of the value which has been accepted by the Ministry of Health and Welfare of Japan (MHW). 2) The minimum effective dose to bacterial growth in food can not be lowered below the standard usage level with MHW determined, because the inactivation factor in food, decreasing effectivity to 1/20, must be taken into consideration. 3) In view of these two facts, AF-2 is found to be unacceptable as a food additive. 4) Great importance must also be attached to the possibility of mutagenicity and carcinogenicity of AF-2, pointed out recently. Both neurotoxicity and dermatitis observed in tofu (soybean curd) makers are also memtioned. (+info)
Synthesis of styrenes through the biocatalytic decarboxylation of trans-cinnamic acids by plant cell cultures.
A novel method for producing styrenes from trans-cinnamic acids was developed. When trans-cinnamic acid was incubated with plant cell cultures at room temperature, styrene was obtained. 4-Hydroxy-3-methoxystyrene (2a), 3-nitrostyrene (2f) and furan (2g) were synthesized quantitatively. (+info)
Review article: alternative antibacterial agents for Helicobacter pylori eradication.
Standard eradication therapies against Helicobacter pylori appear to be effective in most cases, but in clinical practice a failure rate higher than the 5-10% reported in clinical trials is often observed. Among the various reasons responsible for therapeutic failure, antibiotic resistance is becoming a major issue in some countries. A range of different antibacterial agents is currently under investigation: several macrolides, new fluoroquinolones, furazolidone and rifabutin. Although not formally tested in refractory cases, azithromycin, spiromycin, levofloxacin and furazolidone represent the most promising antibacterial agents for possible inclusion in eradication regimens. Rifabutin has been evaluated in H. pylori infections resistant to standard therapies. Although very effective, the drug is expensive and its use should be restricted to the most difficult cases to avoid the development of rifabutin resistance in Mycobacterium spp. (+info)
Damage to mammalian cell DNA by nitrofurans.
Maximum rates of nitrofuran reduction by intact mammalian cells and homogenates of mouse liver are obtained under anaerobic conditions, although significant reduction does occur with gas mixtures containing 5% oxygen and less. Single-strand breaks in DNA, measured as a decrease in the sedimentation constant on alkaline sucrose gradients, are produced in mammalian L929, KB, AND BHK-21 cells in vitro and Ehrlich ascites cells in vivo by several nitrofuran derivatives under hypoxic conditons. (+info)
Enzymes associated with reductive activation and action of nitazoxanide, nitrofurans, and metronidazole in Helicobacter pylori.
Nitazoxanide (NTZ) is a redox-active nitrothiazolyl-salicylamide prodrug that kills Helicobacter pylori and also many anaerobic bacterial, protozoan, and helminthic species. Here we describe development and use of a spectrophotometric assay, based on nitroreduction of NTZ at 412 nm, to identify H. pylori enzymes responsible for its activation and mode of action. Three enzymes that reduce NTZ were identified: two related NADPH nitroreductases, which also mediate susceptibility to metronidazole (MTZ) (RdxA and FrxA), and pyruvate oxidoreductase (POR). Recombinant His-tagged RdxA, FrxA, and POR, overexpressed in nitroreductase-deficient Escherichia coli, each rapidly reduced NTZ, whereas only FrxA and to a lesser extent POR reduced nitrofuran substrates (furazolidone, nitrofurantoin, and nitrofurazone). POR exhibited no MTZ reductase activity either in extracts of H. pylori or following overexpression in E. coli; RdxA exhibited no nitrofuran reductase activity, and FrxA exhibited no MTZ reductase activity. Analysis of mutation to rifampin resistance (Rif(r)) indicated that NTZ was not mutagenic and that nitrofurans were only weakly mutagenic. Alkaline gel DNA electrophoresis indicated that none of these prodrugs caused DNA breakage. In contrast, MTZ caused DNA damage and was strongly mutagenic. We conclude that POR, an essential enzyme, is responsible for most or all of the bactericidal effects of NTZ against H. pylori. While loss-of-function mutations in rdxA and frxA produce a Mtz(r) phenotype, they do not contribute much to the innate susceptibility of H. pylori to NTZ or nitrofurans. (+info)