Dual-targeted anti-TB/anti-HIV heterodimers

- We synthetized five heterodimers of an anti-TB molecule and an anti-HIV molecule.
- These compounds inhibited growth of M. tuberculosis and replication of HIV in a cell line and in human lymphoid tissue.
- One compound that combined the strongest anti-bacterial and anti-viral effects was neither cytopathic nor cytostatic.
- This compound is a leading candidate for future development and in vivo testing.

HIV and M. tuberculosis are two intersecting epidemics making the search for new dual action drugs against both pathogens extremely important. Here, we report on the synthesis and suppressive activities of five dual-targeted HIV/TB compounds. These compounds are heterodimers of AZT, as anti-HIV molecules, and 5-substituted uracil derivatives, as anti-TB molecules. We found that these compounds inhibit the growth of M. tuberculosis and suppress the replication of HIV in human cell cultures and human lymphoid tissues ex vivo. We identified one particular heterodimer that inhibited both HIV and the drug-resistant TB strain MS-115 most potently. This compound demonstrated low toxicity and had no cytostatic effect on cells in culture, constituting an ideal candidate for future development and further in vivo testing.