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.

Anti-infective potential of catechins and their derivatives against viral hepatitis

“…Interestingly, EGC which has been reported no obvious inhibitory activity on HCV infection showed anti-HCV activities similar to that of EGCG in this study. Catechin derivatives [ 18 ] that contain several additional galloyl moieties have been synthesized and evaluated for their in vitro inhibitory effects against HCV infection using HCV subgenomic replicon. Based on the structure-activity relationship between synthetic compounds, the 2,3,4-trihydroxybenzoyl moiety in tripodal compounds and 12 polymethylene in linear compounds provides better antiviral activities than 3,4,5-trihydroxybenzoyl moiety in natural green catechins.…”

Synthesis and Spectroscopic Characterization of bis-Swallow Tailed Mesogen

“…The mixture was heated at 160 ͦ C for 5 hour. The reaction mixture was allowed to reach room temperature and then was cooled by a water-ice bath to give a precipitate that was filtered and washed with gently quantities of diethyl ether (9) . acid] (0.003mol) with 10 mL pyridine were stirred for overnight in an ice bath.…”

Therapeutic and Prophylactic Potential of Morama (Tylosema esculentum): A Review

“…A number of the components of morama beans are known to inhibit enteroviruses. Additionally, some of the components of morama bean testae are reported to inhibit the replication of common viral infections, particularly gallic acid against hepatitis C virus (Rivero‐Buceta et al ., ) and HIV (Kratz et al ., ), vanillic acid against HIV (Kim et al ., ), hesperidin against influenza virus (Saha et al ., ), fisetin against dengue virus (Zandi et al ., ), quercetin against Mayaro fever virus (dos Santos et al ., ) and tannins against influenza virus and Coxsackie virus (Abdel‐Mageed et al ., ).…”