title: Linear and branched alkyl-esters and amides of gallic acid and other (mono-, di- and tri-) hydroxy benzoyl derivatives as promising anti-HCV inhibitors.
abstract: Linear and branched compounds that contain two, three or five units of galloyl (3,4,5-trihydroxybenzoyl) or its isomer 2,3,4-trihydroxybenzoyl, as well as other mono- or dihydroxybenzoyl moieties have been synthesized. These molecules have been evaluated for their in vitro inhibitory effects against a wide panel of viruses showing preferential activity against HIV and HCV. Our structure-activity relationship studies demonstrated that the 2,3,4-trihydroxybenzoyl moiety provides better antiviral activities than the galloyl (3,4,5-trihydroxybenzoyl) moiety that is present in natural green tea catechins. This observation can be of interest for the further rational exploration of compounds with anti-HCV/HIV properties. The most notable finding with respect to HIV is that the tripodal compounds 43 and 45, with three 2,3,4-trihydroxybenzoyl moieties, showed higher activities than linear compounds with only one or two. With respect to HCV, the linear compounds, 52 and 41, containing a 12 polymethylene chain and two 2,3 di- or 2,3,4 tri-hydroxybenzoyl groups respectively at the ends of the molecule showed good antiviral efficiency. Furthermore, the anti-HCV activity of both compounds was observed at concentrations well below the cytotoxicity threshold. A representative member of these compounds, 41, showed that the anti-HCV activity was largely independent of the genetic make-up of the HCV subgenomic replicon and cell lines used.
authors.affiliation: Instituto de Química Médica (IQM-CSIC), Juan de la Cierva 3, 28006 Madrid, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Rivero-Buceta
authors.affiliation: Instituto de Química Médica (IQM-CSIC), Juan de la Cierva 3, 28006 Madrid, Spain; ABG Patentes, Avenida de Burgos 16D, 28036 Madrid, Spain.
authors.forename: Paula
authors.initials: P
authors.lastname: Carrero
authors.affiliation: Instituto de Química Médica (IQM-CSIC), Juan de la Cierva 3, 28006 Madrid, Spain; Centro de Química Orgánica "Lora-Tamayo" (CSIC), Juan de la Cierva 3, 28006 Madrid, Spain.
authors.forename: Elisa G
authors.initials: EG
authors.lastname: Doyagüez
authors.affiliation: Instituto de Química Médica (IQM-CSIC), Juan de la Cierva 3, 28006 Madrid, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Madrona
authors.affiliation: Instituto de Química Médica (IQM-CSIC), Juan de la Cierva 3, 28006 Madrid, Spain.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Quesada
authors.affiliation: Instituto de Química Médica (IQM-CSIC), Juan de la Cierva 3, 28006 Madrid, Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: Camarasa
authors.affiliation: Instituto de Química Médica (IQM-CSIC), Juan de la Cierva 3, 28006 Madrid, Spain.
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Peréz-Pérez
authors.affiliation: Rega Institute for Medical Research, KU Leuven, B-3000 Leuven, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Leyssen
authors.affiliation: Rega Institute for Medical Research, KU Leuven, B-3000 Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Paeshuyse
authors.affiliation: Rega Institute for Medical Research, KU Leuven, B-3000 Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.affiliation: Rega Institute for Medical Research, KU Leuven, B-3000 Leuven, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Neyts
authors.affiliation: Instituto de Química Médica (IQM-CSIC), Juan de la Cierva 3, 28006 Madrid, Spain. Electronic address: anarosa@iqm.csic.es.
authors.forename: Ana
authors.initials: A
authors.lastname: San-Félix
mesh_terms: D000478:Alkylation; D000577:Amides / Q000737:chemistry*; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004952:Esters / Q000737:chemistry*; D005707:Gallic Acid / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006678:HIV / Q000187:drug effects; D016174:Hepacivirus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D000998:Antiviral Agents; D004952:Esters; D005707:Gallic Acid
keywords: AIDS; Antiviral agents; HCV; HIV; Polyphenols