Synthesis and antiviral evaluation of 7-O-arylmethylquercetin derivatives against SARS-associated coronavirus (SCV) and hepatitis C virus (HCV)

Abstract

Aryl diketoacid (ADK) is well known for antiviral activity which can be enhanced by introduction of an aromatic arylmethyl substituent. A natural flavonoid quercetin has a 3,5-dihydroxychromone pharmacophore which is in bioisosteric relationship with the 1,3-diketoacid moiety of the ADK. Thus, it was of our interest to test the antiviral activity of the quercetin derivatives with an arylmethyl group attached. In this study, we prepared a series of the 7-O-arylmethylquercetin derivatives with various aromatic substituents and evaluated their antiviral activity against the SARS-associated coronavirus (SARS-CoV, SCV) as well as hepatitis C virus (HCV). Single difference in the aromatic substituent fine-tuned the biological activity of the 7-O-arylmethylquercetin derivatives to result in two different classes of derivatives selectively active against SCV and HCV.

The Inhibitory Activities and Antiviral Mechanism of Medicinal Plant Ingredient Quercetin Against Grouper Iridovirus Infection

“…Scale bar: 50 μm. October 2020 | Volume 11 | Article 586331 oils against HSV type 2 (Koch et al, 2008), flavonoids quercetin against Zika virus, SARS-associated coronavirus, hepatitis C virus (HCV), and influenza A virus (Park et al, 2012;Wu et al, 2015;Wong et al, 2017). In the previous study, we explored the antiviral effects of some I. verum extracts against SGIV.…”

“…Modern pharmacology studies have proved that these active compounds possess diverse pharmacological actions, including antiviral, antimicrobial, insecticidal, analgesic, antioxidant, sedative, and convulsive activities ( Chaubey, 2008 ; Dzamic et al, 2009 ; Wang et al, 2011 ; Liu et al, 2020b ). Some I. verum ingredients especially have excellent antiviral effects, such as sesquiterpenes against hepatitis B virus and HIV ( Song et al, 2007 ; Liu et al, 2015 ), essential oils against HSV type 2 ( Koch et al, 2008 ), flavonoids quercetin against Zika virus, SARS-associated coronavirus, hepatitis C virus (HCV), and influenza A virus ( Park et al, 2012 ; Wu et al, 2015 ; Wong et al, 2017 ). In the previous study, we explored the antiviral effects of some I. verum extracts against SGIV.…”

Roles of flavonoids against coronavirus infection

“…The same group later published the synthesis of several 7- O -arylmethylquercetin derivatives. Three of them, with 3″-Cl, 3″-CN, and 4″-Cl substituent on arylmethyl group, tested in this study showed inhibitory activity against SARS-CoV NTPase/helicase ranging between 2.7 and 5.2 μM, the same order of magnitude of the parental compound [ 63 ]. The NSP13 helicase possesses a dsDNA unwinding activity as well as an ATPase activity allowing the helicase to translocate along with the nucleic acids by hydrolyzing ATP.…”

Synthesis and In vitro Leishmanicidal Activities of Six Quercetin Derivatives

“…13 C-NMR (DMSO-D6) δ: 175.9, 163.3, 160.4, 155.9, 147.9, 147.4, 147.1, 145.05, 144.05, 136.06, 128.3, 128.3, 123.7, 123.7, 123.5, 121.75, 119.98, 115.56, 115.2, 104.3, 97.97, 92.85, 68.58, 39.84, 39.63, 39.4, 39.2, and 39; IR (KBr); ν max : 3404, 2922, 1655, 1595, 1522, 1346, and 1165 cm −1 ; and ESI-MS ( m /z): 436 [M-H] − . [ 9 ]…”