Synthesis and Anti-influenza Activities of Novel Baicalein Analogs

Abstract

A series of novel flavones derivatives were synthesized based on modification of the active ingredients of a traditional Chinese medicine Scutellaria baicalensis GEORGI and screened for anti-influenza activity. The synthetic baicalein (flavone) analogs, especially with the B-rings substituted with bromine atoms, were much more potent than oseltamivir or ribavirin against H1N1 Tamiflu-resistant (H1N1 TR) virus and usually with more favorable selectivity. The most promising were 5b, 5c, 6b and 6c, all displaying an 50% effective concentration (EC 50 ) at around 4.0-4.5 µM, and a selective index (SI 50% cytotoxic concentration (CC 50 )/ EC 50 )>70. For seasonal H3N2-infected influenza virus, both 5a and 5b with SI >17.3 indicated superior to ribavirin. The flavonoids having both not-naturally-occurring bromo-substituted B-rings and appropriate hydroxyls positioning on the A-rings might be critical in determining the activity and selectivity against H1N1-Tamiflu-resistant infected influenza viruses.

Flavonoids: promising natural compounds against viral infections

“…T cells and act as a potent inducer of IFN-c during influenza virus infection [19]. Recently, novel baicalein analogs with B-rings substituted with bromine atoms demonstrated extremely potent activity against influenza H1N1 Tamiflu-resistant virus, indicating that baicalein and its analogs can be favorable alternatives in the management of Tamiflu-resistant viruses [21]. In vitro replication of HIV-1 was suppressed by baicalin when infected cells were treated during the early stage of the virus replication cycle [66].…”

Synthesis and Antibacterial Screening of Novel Fluorine Containing Heterocycles

“…These can serve as a key synthon for various heterocycles like flavones, pyrazolines and aurones. Flavones are known for their antimicrobial 23 , antiviral 24 , anticancer 25 and antiinflammatory 26 properties. Literature data also revealed that chromones substituted with pyrazole nucleus exhibit antimicrobial 27,28 activities.…”

Wogonin, a flavonoid isolated from Scutellaria baicalensis, has anti-viral activities against influenza infection via modulation of AMPK pathways

“…Recent studies have focused on the anti-influenza activities of Scutellaria baicalensis-derived compounds and derivatives. In particular, the anti-influenza activities of baicalein and baicalin, components of the roots of Scutellaria baicalensis, have been reported by several groups (Chen et al, 2011;Hour et al, 2013;Sithisarn et al, 2013;Chung et al, 2014;Nayak et al, 2014). Baicalin exerts its anti-influenza virus activity by modulating viral non-structural protein 1 (NS1), which results in the up-regulation of interferon (IFN)induced antiviral signaling and reduced phosphoinositide 3-kinase/Akt (PI3K/Akt) signaling in A549 cells (Nayak et al, 2014).…”