The present invention involves compounds that that demonstrate predominant activity against replicating Mtb, non-replicating Mtb, or both replicating and non-replicating Mtb.
Tuberculosis (TB) is the leading cause of death amongst infectious diseases worldwide. Approximately 2 million people per year die of TB and up to one third of the world's population (~2 billion people) harbor latent TB. Tuberculosis caused by multiple- and extremely-drug resistant (MDR and XDR, respectively) Mycobacterium tuberculosis (Mtb) is becoming more common. XDR-Mtb has a mortality rate of over 80%. It is also extremely difficult to treat with current antibiotics - chemotherapy can last from 6 months to 2 years. The long duration of chemotherapy required to treat TB is thought to be due to non-replicating Mtb that are phenotypically resistant to chemotherapy by factors of host immunity. Standard antibiotics used to treat TB, such as isoniazid, have poor to no activity against non-replicating Mtb. Failure to eradicate non-replicating Mtb by standard chemotherapy leaves the human host susceptible to recrudescence of latent bacilli and development of TB. Thus, the development of a new drug that more effectively treats TB and, specifically, targets non-replicating Mtb, would have valuable industry applications.
-Inclusion of compounds in standard antimicrobial therapy used to treat human TB
-Administration of compounds in combination with treatment for other disorders commonly accompanied by TB
The present invention involves compounds that demonstrate predominant activity against replicating Mtb, non-replicating Mtb, or both replicating and non-replicating Mtb. Activity was tested in an environment that simulates physiological stresses found within the human body. Thus, these compounds have the potential to treat TB more effectively than current drugs. These compounds could eventually be included in standard antimicrobial therapy used to treat human TB.
-Increased efficacy of TB treatment
-Activity against replicating and non-replicating Mtb
-Potential to decrease duration of chemotherapy to treat TB