Structure–activity studies of (−)-epigallocatechin gallate derivatives as HCV entry inhibitors

Bhat, Rohit; Adam, Amna T.; Lee, Jungeun Jasmine; Deloison, Gaspard; Rouillé, Yves; Séron, Karin; Rotella, David P.

doi:10.1016/j.bmcl.2014.07.051

Cited by 16 publications

(5 citation statements)

References 12 publications

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“…Regarding these biological properties, EGCG ( 1 ) has been reported to possess a broad spectrum of antiviral activities against DNA viruses such as herpes simplex virus (HSV; Herpesviridae ) [5,6,7,8,9,10,11], adenovirus ( Adenoviridae ) [10,12], human papilloma virus (HPV; Papovaviridae ) [13], and hepatitis B virus (HBV; Hepadnaviridae ) [14], and against (+)-RNA viruses such as hepatitis C virus (HCV; Flaviviridae ) [10,15,16,17,18,19], Zika virus (ZIKV; Flaviviridae ) [20,21,22,23], dengue virus (DENV; Flaviviridae ) [23,24], West Nile viruses (WNV; Flaviviridae ) [23], Chikungunya virus (CHIKV; Togaviridae ) [25], and Porcine Reproductive and Respiratory virus (PRRS; Atteriviridae ) [26], and (−)-RNA viruses such as human immunodeficiency virus (HIV; Retroviridae ) [27,28,29,30,31,32,33,34,35,36], Ebola virus (EBOV; Filoviridae ) [37] and influenza virus ( Orthomyxoviridae ) [2,10,38,39,40,41,42,43,44,45,46,47,48]. …”

Section: Introductionmentioning

confidence: 99%

Antiviral Mechanism of Action of Epigallocatechin-3-O-gallate and Its Fatty Acid Esters

2018

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Epigallocatechin-3-O-gallate (EGCG) is the major catechin component of green tea (Cameria sinensis), and is known to possess antiviral activities against a wide range of DNA viruses and RNA viruses. However, few studies have examined chemical modifications of EGCG in terms of enhanced antiviral efficacy. This paper discusses which steps of virus infection EGCG interferes with, citing previous reports. EGCG appears most likely to inhibits the early stage of infections, such as attachment, entry, and membrane fusion, by interfering with viral membrane proteins. According to the relationships between structure and antiviral activity of catechin derivatives, the 3-galloyl and 5′-OH group of catechin derivatives appear critical to antiviral activities. Enhancing the binding affinity of EGCG to virus particles would thus be important to increase virucidal activity. We propose a newly developed EGCG-fatty acid derivative in which the fatty acid on the phenolic hydroxyl group would be expected to increase viral and cellular membrane permeability. EGCG-fatty acid monoesters showed improved antiviral activities against different types of viruses, probably due to their increased affinity for virus and cellular membranes. Our study promotes the application of EGCG-fatty acid derivatives for the prevention and treatment of viral infections.

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Section: Introductionmentioning

confidence: 99%

Antiviral Mechanism of Action of Epigallocatechin-3-O-gallate and Its Fatty Acid Esters

2018

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“…The prenylated benzamide present in NB was shown to represent an ideal replacement for the gallic acid moiety of EGCG and resulted in ~15-fold improvement in antiproliferative activity and ultimately led to the development of compound 21 (MCF-7, IC 50 = 4 μM). Further studies by Bhat and coworkers confirmed the non-essential nature of the B- and D-ring phenols and established the ester linker connecting the C- and D-rings could be replaced with an amide or sulfonamide without compromising anticancer activity (Bhat et al, 2014). How these modifications affect interactions with Hsp90 remain unknown.…”

Section: Novel Hsp90 Inhibitors: Beyond the Usual Suspectsmentioning

confidence: 99%

Anticancer Inhibitors of Hsp90 Function

Garg

Khandelwal

Blagg

2016

Advances in Cancer Research

127

109

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The 90-kDa heat-shock protein (Hsp90) is a molecular chaperone responsible for the stability and function of a wide variety of client proteins that are critical for cell growth and survival. Many of these client proteins are frequently mutated and/or overexpressed in cancer cells and are therefore being actively pursued as individual therapeutic targets. Consequently, Hsp90 inhibition offers a promising strategy for simultaneous degradation of several anticancer targets. Currently, most Hsp90 inhibitors under clinical evaluation act by blocking the binding of ATP to the Hsp90 N-terminal domain and thereby, induce the degradation of many Hsp90-dependent oncoproteins. Although, they have shown some promising initial results, clinical challenges such as induction of the heat-shock response, retinopathy, and gastrointestinal tract toxicity are emerging from human trials, which constantly raise concerns about the future development of these inhibitors. Novobiocin derivatives, which do not bind the chaperone’s N-terminal ATPase pocket, have emerged over the past decade as an alternative strategy to inhibit Hsp90, but to date, no derivative has been investigated in the clinical setting. In recent years, a number of natural or synthetic compounds have been identified that modulate Hsp90 function via various mechanisms. These compounds not only offer new chemotypes for the development of future Hsp90 inhibitors but can also serve as chemical probes to unravel the biology of Hsp90. This chapter presents a synopsis of inhibitors that directly, allosterically, or even indirectly alters Hsp90 function, and highlights their proposed mechanisms of action.

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“…Similarly, anhydro‐dihydro‐artemisinin potentiated antiviral activity against HCV (Blazquez et al, 2013). In order to find more effective EGCG derivatives as HCV entry inhibitors, Bhat et al (2014) identified 3,4‐difluoro analogue of EGCG with less cytotoxicity and enhanced anti‐HCV potency (Bhat et al, 2014). Structure–activity relationship (SAR) studies demonstrated that 2,3 di‐ or 2,3,4‐trihydroxybenzoyl moiety provided better antiviral activity against HCV than the galloyl (3,4,5‐trihydroxybenzoyl) moiety that is present in natural green tea catechins (Rivero‐Buceta et al, 2015).…”

Section: Synthetic Derivatives Of Phytochemicals With Anti‐hcv Activitymentioning

confidence: 99%

Medicinal plant molecules against hepatitis C virus: Current status and future prospect

Mandal¹,

Hazra

2023

Phytotherapy Research

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Hepatitis C virus (HCV), a global malady, causes acute and chronic hepatitis leading to permanent liver damage, hepatocellular carcinoma, and death. Modern anti‐HCV therapies are efficient, but mostly inaccessible for residents of underdeveloped regions. To innovate more effective treatments at affordable cost, medicinal plant‐based products need to be explored. The aim of this article is to review plant constituents in the light of putative anti‐HCV mechanisms of action, and discuss existing problems, challenges, and future directions for their potential application in therapeutic settings. One hundred sixty literatures were collected by using appropriate search strings via scientific search engines: Google Scholar, PubMed, ScienceDirect, and Scopus. Bibliography was prepared using Mendeley desktop software. We found a substantial number of plants that were reported to inhibit different stages of HCV life cycle. Traditional medicinal plants such as Phyllanthus amarus Schumach. and Thonn., Eclipta alba (L.) Hassk., and Acacia nilotica (L.) Delile exhibited strong anti‐HCV activities. Again, several phytochemicals such as epigallocatechin‐3‐gallate, honokilol, punicalagin, and quercetin have shown broad‐spectrum anti‐HCV effect. We have presented promising phytochemicals like silymarin, curcumin, glycyrrhizin, and camptothecin for nanoparticle‐based hepatocyte‐targeted drug delivery. Nevertheless, only a few animal studies have been performed to validate the anti‐HCV effect of these plant products. Again, insufficient clinical evaluation of the safety and effectiveness of herbal medications remain a problem. Selected plants products could be developed as novel therapeutics for HCV patients only after scrupulous evaluation of their safety and efficacy in a clinical set‐up.

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Structure–activity studies of (−)-epigallocatechin gallate derivatives as HCV entry inhibitors

Cited by 16 publications

References 12 publications

Antiviral Mechanism of Action of Epigallocatechin-3-O-gallate and Its Fatty Acid Esters

Antiviral Mechanism of Action of Epigallocatechin-3-O-gallate and Its Fatty Acid Esters

Anticancer Inhibitors of Hsp90 Function

Medicinal plant molecules against hepatitis C virus: Current status and future prospect

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