Antiretroviral activity of metal-chelating HIV-1 integrase inhibitors

• The chelating properties of some HIV integrase inhibitors are investigated.
• Their metal complexes are characterized, also by isothermal titration calorimetry.
• The compounds have an activity in the nanomolar range in HIV-infected cells.
• They are also tested for inhibition of RT-associated RNase H catalytic activity.

Data regarding the activity of metal complexes against HIV virus in cell are surprisingly scarce. In this study, we present the antiviral activity against HIV-infected cells of different types of chelating ligands and of their metal complexes. In particular, the carboxamide chelating scaffold and the corresponding coordination compounds demonstrated an interesting antiviral profile in the nanomolar range. These molecules inhibit not only HIV integrase catalytic activity, but they also interfere with the function of the RNase H component of the HIV reverse transcriptase. Here we also discuss the thermodynamic characterization in solution of the metal complexes of the most active ligands, affording to the best of our knowledge for the first time this type of data for complexes with anti-HIV activity.

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