Chumillas, SergiBedoya Del Olmo, Luis MiguelGallego, José2024-05-062024-05-062003-10-11Chumillas, S.; Loharch, S.; Beltrán, M.; Szewczyk, M.P.; Bernal, S.; Puertas, M.C.; Martinez-Picado, J.; Alcamí, J.; Bedoya, L.M.; Marchán, V.; et al. Exploring the HIV-1 Rev Recognition Element (RRE)–Rev Inhibitory Capacity and Antiretroviral Action of Benfluron Analogs. Molecules 2023, 28, 7031. https://doi.org/10.3390/molecules2820703110.3390/molecules28207031https://hdl.handle.net/20.500.14352/103750Artículo firmado por 11 autores. 2023 Descuento MDPIHuman immunodeficiency virus-type 1 (HIV-1) remains one of the leading contributors to the global burden of disease, and novel antiretroviral agents with alternative mechanisms are needed to cure this infection. Here, we describe an exploratory attempt to optimize the antiretroviral properties of benfluron, a cytostatic agent previously reported to exhibit strong anti-HIV activity likely based on inhibitory actions on virus transcription and Rev-mediated viral RNA export. After obtaining six analogs designed to modify the benzo[c]fluorenone system of the parent molecule, we examined their antiretroviral and toxicity properties together with their capacity to recognize the Rev Recognition Element (RRE) of the virus RNA and inhibit the RRE-Rev interaction. The results indicated that both the benzo[c] and cyclopentanone components of benfluron are required for strong RRE-Rev target engagement and antiretroviral activity and revealed the relative impact of these moieties on RRE affinity, RRE-Rev inhibition, antiviral action and cellular toxicity. These data provide insights into the biological properties of the benzo[c]fluorenone scaffold and contribute to facilitating the design of new anti-HIV agents based on the inhibition of Rev function.engAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/journal article1420-3049https//doi.org/10.1007/10.3390/molecules28207031https://www.mdpi.com/1420-3049/28/20/7031open access615.1Antiviral drug discoveryBenfluronBenzo[c]fluorenoneHuman immunodeficiency virus type 1RevRNAFarmacología (Farmacia)3209 Farmacología