Design, synthesis, and anti-integrase activity of catechol–DKA hybrids

Following the discovery of diketoacid-containing compounds as HIV-1 integrase (IN) inhibitors, a plethora of new molecules have been published leading to four drugs under clinical trial. In an attempt to rationally design new dimeric diketoacids (DKAs) targeting two divalent metal ions on the active site of IN, potent inhibitors against purified IN were found with varied selectivity for strand transfer. In this context, we designed and synthesized a new series of catechol–DKA hybrids. These compounds presented micromolar anti-integrase activities with moderate antiviral properties.

We designed and synthesized a new series of catechol–diketoacid hybrids as HIV-1 integrase inhibitors. The strand transfer/3′-processing selectivity was affected by the presence of the catechol moiety. These compounds presented micromolar anti-integrase activities with moderate antiviral properties.Figure optionsDownload as PowerPoint slide