Design, synthesis and biological evaluation of gentiopicroside derivatives as potential antiviral inhibitors

Abstract

Based on classical drug design theory, a novel series of gentiopicroside derivatives was designed and synthesized. All synthesized compounds were then biologically evaluated for their inhibition of influenza virus and anti-HCV activity in vitro. Some of the gentiopicroside derivatives, such as 11a, 13d and 16 showed interesting anti-influenza virus activity with IC at 39.5 μM, 45.2 μM and 44.0 μM, respectively. However, no significant anti-HCV activity was found for all of gentiopicroside derivatives. The preliminary results indicate that modification of the sugar moiety on gentiopicroside was helpful for enhancing the anti-influenza activities. Our works demonstrate the importance of secoiridoid natural products as new leads in the development of potential antiviral inhibitors.

Development of anti‐influenza agents from natural products

“…The preliminary results indicated that modification of the sugar moiety on 5 was essential for the enhanced biological potency. 43 The chemical structures of 3−8 are shown in Figure 5.…”

“…Thus, compound 42 might be a potential therapeutic anti-influenza agent exerting anti-inflammatory activities. 64 Two natural triterpenoid acids, meristotropic acid (43) and its methyl ester (44), as well as their synthetic derivatives, were tested for activities against influenza viruses A and B in MDCK cell cultures and a mouse model of lethal influenza pneumonia. Among them, compounds 43 and 44 were the most active against H1N1 rimantadine-resistant virus A/PR/8/34 (CTD 50 = 683.7 μM), more potent than the reference rimantadine (CTD 50 = 379.8 μM), suggesting that they might have potential for further development as new effective anti-influenza drugs.…”

“…Among them, compounds 6 − 8 showed interesting antiviral activities against H1N1 (A/WSN/33) with IC 50 values of 39.5, 45.2, and 44.0 μM, respectively. The preliminary results indicated that modification of the sugar moiety on 5 was essential for the enhanced biological potency 43 …”

Development of gastroretentive floating granules with gentian root extract by hot-melt granulation

“…xanthones (isogentisin, gentioside, gentisin), and flavonoids (isovitexin, isoorientin) (Šavikin et al, 2015; Živković et al, 2019). Gentiopicroside is the dominant bioactive compound in the gentian root extract with choleretic, hepatoprotective, adaptogenic and anti-inflammatory activities (Wu et al, 2017). However, there are obstacles, due to suboptimal pharmacokinetic properties of gentiopicroside, such as short elimination half-life (2.8 h) and low bioavailability (39.6 %), reported after animal studies (Wang et al, 2004) that limit its bioactive potential.…”

Gentiopicroside Ameliorates Diabetic Peripheral Neuropathy by Modulating PPAR- Γ/AMPK/ACC Signaling Pathway

“…It is one of the most common herbal medicines in China [12]. Animal experiments have revealed its pharmacological effects such as choleretic, antihepatotoxic, adaptogenic and anti-inflammatory activities [12][13][14]. Recently, Gentiopicroside is found to exert on the central nervous system with analgesic effect [15].…”