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Dual-targeted anti-TB/anti-HIV heterodimers.


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 constitute heterodimers of AZT, as anti-HIV molecules, and 5-arylaminouracil derivatives or 2'-deoxyuridine monophosphates analogues, 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 most potently both HIV and the drug-resistant TB strain MS -115. This compound demonstrated low toxicity and had no cytostatic effect on cells in culture. This is a leading candidate for future development and further in vivo testing.