2026-06-30T03:03:41Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/168092024-09-27T20:58:48Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609

00925njm 22002777a 4500 dc Chumillas, Sergi author Loharch, Saurabh author Beltran, Manuela author Szewczyk, Mateusz P author Bernal, Silvia author Puertas, Maria C author Martinez-Picado, Javier author Alcamí, José author Bedoya, Luis M author Marchán, Vicente author Gallego, José author 2023-10-11 Human 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. Molecules. 2023 Oct 11;28(20):7031. 10.3390/molecules28207031 1420-3049 Molecules (Basel, Switzerland) 37894510 http://hdl.handle.net/20.500.12105/16809 Antiviral drug discovery Benfluron Benzo[c]fluorenone Human immunodeficiency virus type 1 Rev RNA Exploring the HIV-1 Rev Recognition Element (RRE)-Rev Inhibitory Capacity and Antiretroviral Action of Benfluron Analogs