Tryptanthrin is a natural product of a Chinese/Taiwanese medicinal plant. This compound and its relatives (collectively known as the tryptanthrins) have been extensively explored as anti-bacterial, anti-malarial and anti-cancer agents. During the 1990s, tryptanthrins emerged as potential anti-tuberculosis therapeutics with the ability to prevent growth of both drug sensitive and drug resistant tuberculosis bacteria. However, due to the inability of the particular compounds tested to kill bacteria in mouse models of TB, tryptanthrins were not pursued. Other challenges to development of tryptanthrins as anti-tuberculosis agents include their insolubility and probable toxicity. In addition, the cellular target of tryptanthrins is not known. The goal of this program is to identify tryptanthrins that combine the ability to kill tuberculosis in mouse models of disease with favorable properties such as low toxicity and thus possess potential for development as TB drugs that are expected to be effective against drug resistant bacteria.