Evaluation of nitrofurantoin combination therapy of metronidazole-sensitive and -resistant Helicobacter pylori infections in mice.
AuthorsJenks PJ, Ferrero RL, Tankovic J, Thiberge JM, Labigne A
JournalAntimicrob Agents Chemother
PubMed ID10991835
'The main objectives of this study were to determine whether the nitroreductase enzyme encoded by the rdxA gene of Helicobacter pylori was responsible for reductive activation of nitrofurantoin and whether a triple-therapy regimen with nitrofurantoin was able to eradicate metronidazole-sensitive and -resistant H. pylori infections from mice. The susceptibilities to ... More
Analysis of rdxA and involvement of additional genes encoding NAD(P)H flavin oxidoreductase (FrxA) and ferredoxin-like protein (FdxB) in metronidazole resistance of Helicobacter pylori.
AuthorsKwon DH, El-Zaatari FA, Kato M, Osato MS, Reddy R, Yamaoka Y, Graham DY
JournalAntimicrob Agents Chemother
PubMed ID10898687
'Metronidazole (Mtz) is a critical ingredient of modern multidrug therapies for Helicobacter pylori infection. Mtz resistance reduces the effectiveness of these combinations. Although null mutations in a rdxA gene that encodes oxygen-insensitive NAD(P)H nitroreductase was reported in Mtz-resistant H. pylori, an intact rdxA gene has also been reported in Mtz-resistant ... More
Design and synthesis of novel pyrrolobenzodiazepine (PBD) prodrugs for ADEPT and GDEPT.
AuthorsSagnou MJ, Howard PW, Gregson SJ, Eno-Amooquaye E, Burke PJ, Thurston DE
JournalBioorg Med Chem Lett
PubMed ID10999476
Three N10-(4-nitrobenzyl)carbamate-protected PBD prodrugs (9a, 9b and 15) have been synthesized and evaluated for potential use in nitroreductase-based ADEPT and GDEPT therapies. An approximately 100-fold activation was observed for the DC-81 prodrug 9a. ... More
Virus-directed enzyme prodrug therapy using CB1954.
AuthorsGrove JI, Searle PF, Weedon SJ, Green NK, McNeish IA, Kerr DJ
JournalAnticancer Drug Des
PubMed ID10834268
The virus-directed enzyme prodrug therapy (VDEPT) anti-cancer 'gene therapy' strategy relies on the use of viral vectors for the efficient delivery to tumour cells of a 'suicide gene' encoding an enzyme which converts a non-toxic prodrug to a cytotoxic agent. The prodrug 5-(aziridin-1-yl)-2,4 dinitrobenzamide, CB1954, has been proposed for use ... More
Use of 2-nitroimidazoles as bioreductive markers for tumour hypoxia.
AuthorsHodgkiss RJ
JournalAnticancer Drug Des
PubMed ID9755725
Tumour hypoxia is thought to contribute to some failures of radiotherapy to achieve local control. Polarographic measurements of tumour oxygenation have been shown to predict clinical response to radiotherapy and patient survival. Hypoxia is also involved in many common types of normal tissue morbidity. However, at present there is no ... More
Metronidazole activation is mutagenic and causes DNA fragmentation in Helicobacter pylori and in Escherichia coli containing a cloned H. pylori RdxA(+) (Nitroreductase) gene.
AuthorsSisson G, Jeong JY, Goodwin A, Bryden L, Rossler N, Lim-Morrison S, Raudonikiene A, Berg DE, Hoffman PS
JournalJ Bacteriol
PubMed ID10960092
Much of the normal high sensitivity of wild-type Helicobacter pylori to metronidazole (Mtz) depends on rdxA (HP0954), a gene encoding a novel nitroreductase that catalyzes the conversion of Mtz from a harmless prodrug to a bactericidal agent. Here we report that levels of Mtz that partially inhibit growth stimulate forward ... More