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.

HIV和结核分枝杆菌是两个交叉的流行病，因此寻找针对这两种病原体的新的双重作用药物极为重要。在这里，我们报告五个双重目标的艾滋病毒/结核病化合物的合成和抑制活性。这些化合物是AZT的异二聚体（作为抗HIV分子）和5取代的尿嘧啶衍生物（作为抗TB分子）。我们发现这些化合物抑制其生长的结核分枝杆菌和抑制HIV的复制在人细胞培养物和人淋巴组织的离体。我们确定了一种最有效地抑制HIV和耐药性TB菌株MS-115的特殊异二聚体。该化合物显示出低毒性并且对培养中的细胞没有细胞抑制作用，是将来开发和进一步体内测试的理想候选者。