biostudies-literatureUnknown51(15)Di Santo RNovel quinolinonyl diketo acids were designed to obtain integrase (IN) inhibitors selectively active against the strand transfer (ST) step of the HIV integration process. Those new compounds are characterized by a single aryl diketo acid (DKA) chain in comparison to 4, a bifunctional diketo acid reported by our group as an anti-IN agent highly potent against both the 3'-processing and ST steps. Compound 6d was the most potent derivative in IN enzyme assays, while 6i showed the highest potency against HIV-1 in acutely infected cells. The selective inhibition of ST suggested the newly designed monofunctional DKAs bind the IN-DNA acceptor site without affecting the DNA donor site.Journal of medicinal chemistry4744-50https://www.ebi.ac.uk/biostudies/studies/S-EPMC2646871biostudies-literatureNovel quinolinonyl diketo acid derivatives as HIV-1 integrase inhibitors: design, synthesis, and biological activities.PMC2646871Roux AMarchand CCrucitti GCLavecchia ARosi FMiele GGalluzzo CMAndreotti MIacovo AMarinelli LNovellino EPalmisano LPommier YDi Giovanni CPalamara ATCosti RDi Santo RAmici RNencioni LfalseNovel quinolinonyl diketo acid derivatives as HIV-1 integrase inhibitors: design, synthesis, and biological activities.Novel quinolinonyl diketo acids were designed to obtain integrase (IN) inhibitors selectively active against the strand transfer (ST) step of the HIV integration process. Those new compounds are characterized by a single aryl diketo acid (DKA) chain in comparison to 4, a bifunctional diketo acid reported by our group as an anti-IN agent highly potent against both the 3'-processing and ST steps. Compound 6d was the most potent derivative in IN enzyme assays, while 6i showed the highest potency against HIV-1 in acutely infected cells. The selective inhibition of ST suggested the newly designed monofunctional DKAs bind the IN-DNA acceptor site without affecting the DNA donor site.2008-01-01T00:00:00Z2008 Aug2025-04-04T07:58:19.38Z2019-03-27T00:20:52ZS-EPMC26468711864674610.1021/jm8001422