A series of compounds containing a nitroimidazopyran nucleus may provide a new treatment for multi-drug resistant tuberculosis, according to US researchers.
Dr C. Kendall Stover (Pathogenesis Corporation, Seattle, Washington) and colleagues report that nitroimidazopyrans, originally investigated as radiosensitizers for use in cancer chemotherapy, were found to possess activity against cultured, replicating M tuberculosis (Nature 2000;405:962). They say that, although a lead compound was found to be mutagenic, which initially discouraged further investigation of the antibacterial activity of the series, bicyclic nitroimidazoles might be potential antitubercular agents. Unlike current antitubercular drugs, nitroimidazopyrans exhibit bacterial activity against both replicating and static M tuberculosis, they say.
A series of nitroimidazopyrans (NAPs) were synthesised based on the lead compound. One NAP, PA-824, was found to exhibit antibacterial activity comparable to that of metronidazole and greater than that of isoniazid. According to Dr Stone et al, poly- and multi-drug resistant strains of M tuberculosis exhibited comparable susceptibility to PA-824, indicating that there was no cross-resistance with current M tuberculosis drugs.
The researchers say that NAPs are "small, orally active molecules that should be amenable to large scale production, making them practical and attractive candidates for the clinical development of a new antitubercular therapy". Nitroimidazopyrans work by inhibiting both protein and cell wall lipid synthesis.